Biomedical subjects

R Armitage

Publications and source records attributed to R Armitage.

At least 37 records · Page 2Linked to original sources

PubMed1997

Relationship between objective and subjective sleep measures in depressed patients and healthy controls.

The purpose of this study was to correlate subjective sleep characteristics based on questionnaire response, and objective sleep EEG features based on polysomnography, in 52 patients with major depressive disorders (MDD) and 49 healthy controls. With the exception of the number of awakenings, subjective and objective sleep measures were strongly correlated in both groups. Patients and controls were able to accurately judge time in bed, total sleep time and sleep latency. However, sleep quality, depth, and how rested participants felt upon awakening were not strongly correlated with objective sleep characteristics, particularly in those with MDD. The findings suggest that estimates such as total sleep time and sleep latency, obtained from questionnaire data, bear a strong resemblance to objective polysomnographic characteristics in both those with MDD and healthy controls. Patients with MDD do not show sleep-state misperceptions although depressed women are more accurate in estimating sleep characteristics than depressed men.

Adult↗

PubMed1997

The effect of fluoxetine on sleep EEG in childhood depression: a preliminary report.

Fluoxetine is associated with substantial objective and subjective sleep disturbance in adults with major depressive disorders. In this preliminary report, the effects of fluoxetine on sleep electroencephologram (EEG) are described in 6 children and adolescents with nonpsychotic major depression. Fluoxetine increased light Stage 1 sleep, the number of arousals and rapid eye movement (REM) density. REM latency was largely unaffected. Oculomotor abnormalities were also evident on treatment, accompanied by an increase in myoclonic activity. Subjective sleep was also disturbed on treatment. These results are in keeping with those observed in depressed adults treated with fluoxetine.

Adolescent↗

PubMed1997

A multicenter, double-blind comparison of the effects of nefazodone and fluoxetine on sleep architecture and quality of sleep in depressed outpatients.

This study was an 8-week, randomized, double-blind, parallel-group investigation that compared the effects of nefazodone and fluoxetine on sleep architecture and on clinician- and patient-rated sleep measures in 43 outpatients with moderate to severe, nonpsychotic major depressive disorder and insomnia. Twenty-two patients received nefazodone 200 mg daily for 1 week, followed by 400 mg daily for 7 weeks. Twenty-one patients received fluoxetine 20 mg daily. Dosage increases (to 500 mg/day for nefazodone and 40 mg/day for fluoxetine) were available after day 29, depending on clinician judgement. Sleep parameters were measured during baseline phase, while patients were unmeasured and symptomatic, and at weeks 2, 4, and 8 of treatment. Nefazodone and fluoxetine were equally effective as antidepressants. However, compared with baseline, nefazodone increased sleep efficiency and reduced the number of awakenings and percent awake and movement time, whereas fluoxetine increased the number of awakenings and did not significantly alter sleep efficiency or percent awake and movement time. Although fluoxetine increased stage 1 sleep and rapid eye movement (REM) latency and reduced total percent REM sleep, nefazodone increased REM sleep, decreased REM latency, and did not alter stage 1 sleep. Differences between treatment groups, based on change from baseline, revealed greater sleep efficiency, fewer awakenings, less percent awake and movement time, less percent stage 1 and more REM sleep, and shorter REM latency for nefazodone compared with fluoxetine. Significantly greater improvement in clinician- and patient-rated sleep disturbance was found with nefazodone compared with fluoxetine. Nefazodone was associated with better sleep quality.

Adult↗

PubMed1997

CD30 ligand in lymphoma patients with CD30+ tumors.

PURPOSE: CD30 ligand (CD30L), which is expressed on resting B and activated T lymphocytes, can induce cell death in several CD30+ cell lines. Patients with CD30+ tumors (Hodgkin's disease and Ki-1+ non-Hodgkin's lymphoma) frequently have elevated soluble CD30 (sCD30) levels in their serum, which correlates with a poor prognosis. The role of sCD30 in protecting tumor cells from CD30L-mediated cell death and the pattern of CD30L expression on human peripheral-blood lymphocytes (PBLs) of normal donors and patients with CD30+ tumors are investigated. MATERIALS AND METHODS: CD30L surface protein expression was determined by two-color flow cytometry on PBLs of patients with CD30+ tumors and normal individuals. CD30L levels were determined on subsets of PBLs before and after stimulation with phytohemagglutinin (PHA), anti-CD3 antibody, or CD40L. sCD30 was measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic activity of membrane-bound CD30L was tested in a CD30+ cell line by the annexin V-binding method. RESULTS: Unstimulated T lymphocytes of normal donors and patients with lymphoma rarely expressed CD30L surface protein, but were able to express it after stimulation with PHA or anti-CD3 antibody. Resting B cells of patients with CD30+ tumors had lower levels of detectable surface CD30L compared with normal donors (mean, 55% and 80.6%, respectively; P = .0008). Patients with high levels of serum sCD30 had lower detectable levels of CD30L on their PBLs (R2 = .72, P = .0008) and exogenous sCD30 blocked membrane-bound CD30L-mediated apoptosis in a CD30+ cell line. CONCLUSION: In patients with CD30+ tumors, sCD30 can decrease the availability of CD30L on PBLs. Blocking the apoptosis-inducing activity of CD30L by its soluble receptor may explain how CD30+ tumors escape immunosurveillance and may be related to the reported poor prognosis of patients who have elevated sCD30 levels.

Adolescent↗

PubMed1996

Production of murine monoclonal antibodies against sulcofuron and flucofuron by in vitro immunisation.

Monoclonal murine anti-pesticide antibodies were produced by in vitro immunisation (IVI) of cultured splenocytes with the pesticides sulcofuron and flucofuron. The majority of both anti-flucofuron and anti-sulcofuron antibodies obtained were of the IgM isotype, rather than IgG. When used in an indirect enzyme-linked immunosorbent assay (ELISA), the antibodies bound to plate coating antigens which incorporated haptens that mimicked moieties present within the immunising pesticide. The antibodies exhibited a high degree of specificity, with the degree of cross-reactivity related to the structural similarity between the hapten present in the plate coating antigen and the moieties present within the immunising pesticide. These results indicated that antibodies specific to both sulcofuron and flucofuron had been produced by IVI. Synthesis of both hapten analogues and immunogens as required for methods based on in vivo immunisation was avoided, whilst antibody production was also comparatively more rapid than traditional methods and minimised animal discomfort.

Animals↗

PubMed1996

Interleukin-15 up-regulates interleukin-2 receptor alpha chain but down-regulates its own high-affinity binding sites on human T and B cells.

The cytokines interleukin (IL)-2 and IL-15 share many biological activities as a consequence of their utilization of the beta and gamma chains of the IL-2 receptor. However, each cytokine binds to a specific receptor alpha chain; IL-2 with low affinity and IL-15 with high affinity. Here, we demonstrate that IL-15, like IL-2, up-regulates expression of IL-2R alpha on human T and B cells, but rapidly down-regulates IL-15 high-affinity binding sites, which represent IL-15R alpha. This leads to a decreased responsiveness to IL-15 as measured by induction of Jak3 tyrosine phosphorylation. These results suggest a mechanism by which IL-15, a product of activated macrophages, may cooperate with IL-2 at the initiation of an immune response and enhance subsequent IL-2 responsiveness during T cell expansion.

B-Lymphocytes↗

PubMed1996

Functional CD40 ligand expression on T lymphocytes in the absence of T cell receptor engagement: involvement in interleukin-2-induced interleukin-12 and interferon-gamma production.

Despite the fact that the great majority of T cells at the site of an inflammatory response are not antigen specific, the mechanisms leading to activation and recruitment of these bystander T cells are poorly understood. We previously reported that soluble (s)CD23 potentiated the interleukin (IL)-2-induced interferon (IFN)-gamma production by T cells co-cultured with autologous monocytes in the absence of T cell receptor (TCR) engagement. Our present data demonstrate that the IL-2-induced IFN-gamma secretion, in the presence but also in the absence of sCD23, is strictly IL-12 dependent, inasmuch as anti-IL-12 antibody abrogated both responses. Most interestingly, anti-CD40 ligand (CD40L) monoclonal antibody significantly inhibited IL-2-induced IL-12 as well as IFN-gamma production. These results suggest that CD40L was expressed on T cells in the absence of TCR engagement. Indeed, purified unstimulated T cells readily expressed CD40L. IL-2 and monocytes did not up-regulate CD40L on resting T cells. It is proposed that low levels of CD40L expression on non-antigen stimulated T cells are sufficient to signal through CD40 molecules on accessory cells and to induce IL-12 secretion, which in turn can synergize with IL-2 for the induction of IFN-gamma production, thus contributing to the inflammatory process.

Adult↗

PubMed1996

Changes in direct current potentials during sleep deprivation.

Previous research reported changes in steady-state brain electrical activity during sleep. However, due to the quasi-linear nature of the Direct Current (DC) changes, artifact contamination was a potential confound. The present study was performed to further explore DC potentials and to help establish its validity. Twenty-five male university students (13 control and 12 sleep-deprived; mean age 19 y (range 17-27 y) served as subjects. During wakefulness, subjects were tested every hour while standard EEG activity recordings were made, as well as DC measurement. Split plot analyses of variance (ANOVAs) revealed that changes in DC activity levels differed between the two groups. The control subjects showed the same pattern of decreasing DC observed previously with a return to baseline levels during waking hours. The sleep-deprived subjects showed a smaller decrease in DC level through the night, followed by a rise in DC level that continued until the end of the 24 h study. It was concluded that DC measurement reflects changes in brain state associated with fatigue that are not attributable to artifactual processes.

Adolescent↗

PubMed1995

Sex differences in the distribution of EEG frequencies during sleep: unipolar depressed outpatients.

Sex differences in period-amplitude-analysed (PAA) sleep EEG activity were evaluated in 20 symptomatic, unmedicated, unipolar, depressed outpatients. 19/20 PAA measures showed significant gender main effects or interactions. Overall, depressed females showed a higher incidence and amplitude of fast frequency, beta activity than males, particularly in the right hemisphere. Moreover, gender effects were also evident in sleep-stage-independent analysis of PAA measures. These findings are in striking contrast to normal controls for whom only slow-frequency activity differentiates males from females. These findings suggest that sex differences are stronger in depressed patients than those observed in normals and that these effects are more pronounced than age-related changes in sleep EEG activity.

Adult↗

PubMed1995

A comparison of period amplitude and power spectral analysis of sleep EEG in normal adults and depressed outpatients.

Three experiments were carried out to evaluate the relationship between two techniques for quantifying electroencephalographic (EEG) data during sleep: period amplitude analysis (PAA) and power spectral analysis (PSA). In Experiment 1, canonical correlations and regression analyses were computed on PSA and PAA data from 40 undergraduate volunteers. The results yielded an average canonical correlation of 0.98. Further, multiple regression analyses demonstrated that the PSA variables accounted for approximately 66% of the variance in the PAA data, whereas PAA variables captured 88% of the variance in the PSA data. Epoch-to-epoch correlations were higher for PAA measures than for PSA data, perhaps indicating greater stability of PSA measures across epochs of sleep. In Experiment 2, PSA and PAA data were compared in 17 unmedicated outpatients with unipolar depression. Canonical correlations and regression analyses indicated that the overlap in variance between PSA and PAA did not exceed 50%, regardless of whether PSA or PAA variables were used as predictors. Epoch-to-epoch correlations between PAA measures were significantly higher than correlations among PSA variables, again suggesting greater stability of PAA data across epochs of sleep. The range of correlations for either data set was, however, substantially lower in the depressed than in the normal group. Experiment 3 evaluated the possibility that filter settings and artifact-rejection procedures had contributed to reduced overlap in PSA-PAA variance and reduced stability in depressed patients. An additional group of eight healthy volunteers served as subjects. Findings in Experiment 3 indicated that methodological differences between Experiments 1 and 2 did not account for the reduced correlations in the depressed group. It was concluded that PSA and PAA data should be comparable in normal subjects but are relatively independent in depressed patients. Epoch-to-epoch correlations were higher for PAA data than those found between PSA measures in both normal subjects and depressed patients, suggesting that PAA may be more stable across sleep epochs. Reduced stability may be a reflection of nonstationarity in the EEG of depressed patients.

Adolescent↗

PubMed1995

Microarchitectural findings in sleep EEG in depression: diagnostic implications.

A 10-year review of sleep electroencephalogram (EEG)-frequency analysis in depression reveals several consistent microarchitectural abnormalities. Decreased delta amplitude or incidence, particularly in the first 100 min of sleep, has been reported. Elevated fast-frequency EEG has been shown in both remitted and symptomatic depressed patients, especially in the right hemisphere. Further, interhemispheric coherence is reduced in both depressed groups. These microarchitectural features may not be present in narcolepsy, obsessive-compulsive disorders, or schizophrenia, despite similarities in sleep-stage characteristics. Collectively, these findings suggest that computer analysis of the sleep EEG may differentiate depressed patients from normal controls and from other clinical populations.

Brain Mapping↗

PubMed1995

Fluoxetine and oculomotor activity during sleep in depressed patients.

The effects of fluoxetine on automated measures of electrooculographic (EOG) and electromyographic (EMG) activity were evaluated in 41 patients with nonpsychotic, major depressive disorder. Sleep EEG evaluations were conducted at baseline, while patients were symptomatic and unmedicated, and following four to five weeks of treatment with fluoxetine (20 mg). The number of eye movements (> 75 microV) and the amplitude of EOG and EMG activity increased significantly on treatment in REM, stages 1, 2, and slow-wave sleep. All patients showed EOG and EMG abnormalities in at least one stage of sleep. Thirty-four percent of patients showed increased EOG and EMG activity on treatment in every sleep stage. It is suggested that fluoxetine-induced oculomotor abnormalities are likely to be the result of increased availability of serotonin and secondary dopaminergic effects.

Adolescent↗

PubMed1995

The distribution of EEG frequencies in REM and NREM sleep stages in healthy young adults.

Period-analyzed electroencephalographic (EEG) activity was evaluated in 11 men and 11 women to explore the distribution of EEG frequencies during sleep and potential gender differences. Significant stage-of-sleep main effects were noted for both incidence and amplitude measures. Power measures seemed to best differentiate between non-rapid eye movement (NREM) stages, although incidence measures showed roughly the same distributions across sleep stages. Beta incidence and amplitude was highest in stage 1 sleep followed in descending order by rapid eye movement (REM), stage 2, and slow-wave sleep (SWS). Delta incidence and amplitude were highest in SWS, with slightly lower values in stage 2. Interestingly, REM was characterized by higher incidence and amplitude delta than those found in stage 1 sleep. EEG variables did not show striking sex differences in any sleep stage, although a global measure of delta power in NREM sleep was higher among women. Hemispheric asymmetries were small throughout REM and NREM stages. These findings suggest that period analysis provides a detailed description of EEG frequency characteristics during sleep but does not reveal dramatic gender differences.

Adult↗

PubMed1994

The effects of fluoxetine on the polysomnogram of depressed outpatients: a pilot study.

The effects of fluoxetine (FLU) and its active metabolite, norfluoxetine (NFLU), on the polysomnogram (PSG) of nine depressed outpatients (eight with major depression; one with bipolar II, depressed phase disorder) were investigated by contrasting PSG values prior to treatment and during administration of FLU. The PSG changes were correlated with daily dose, cumulative dosage, single serum concentrations, and the total area under the serum concentration curve (AUC) of both FLU and NFLU. Fluoxetine clearly increased both stage 1 sleep time and rapid-eye-movement (REM) latency and decreased both percent REM and REM density. With a few exceptions, the cumulative dosage of FLU and the AUC of FLU and NFLU were better predictors of the changes in awake and movement time in the PSG than single-sample concentrations of FLU and NFLU taken at the time of PSG assessment.

Adult↗

PubMed1994

The effects of nefazodone on sleep architecture in depression.

A polysomnographic study was conducted on 10 outpatients with major depression at baseline and during 4 to 8 weeks of open-trial treatment with nefazodone (400 to 600 mg/day). All 10 patients were treatment responders as evidenced by at least 50% reduction from baseline scores on the Hamilton Depression Rating Scale. Nefazodone was associated with significantly decreased wake and movement time and increased minutes and percentage of stage 2 sleep at the expense of light stage 1 sleep. Nefazodone did not increase rapid-eye-movement (REM) latency and it did not suppress REM sleep. In fact, a trend toward increased REM in the second REM period was observed, although decreased REM in the third REM period was also noted. In summary, nefazodone, an effective antidepressant, decreases arousals and wakefulness during sleep and reduces light non-REM sleep. This agent does not appear to suppress REM sleep or prolong REM latency in patients who respond to treatment.

Adult↗

PubMed1994

Case report: menstrual-related very short REM latency in a healthy normal control.

A healthy young woman with regular menstrual cycles and no premenstrual complaints spent 2 consecutive nights in the laboratory at follicular and mid-luteal phases of her cycle. Few differences were noted in sleep parameters with the exception of rapid eye movement (REM) latency, which decreased from 62.5 +/- 0 minutes in the follicular phase to 4.0 +/- 0 minutes in the mid-luteal phase of her cycle, accompanied by an increase in percentage of REM sleep. Very little slow-wave sleep was observed in either phase of the menstrual cycle. The subject refused further study for evaluation of narcolepsy, although she reported no daytime sleepiness. If replicated, these findings suggest phase of the menstrual cycle may primarily influence REM sleep characteristics.

Adult↗

PubMed1993

Recombinant CD40 ligand stimulation of murine B cell growth and differentiation: cooperative effects of cytokines.

The ligand for the B cell surface antigen CD40 was recently cloned from a murine thymoma cDNA library and shown to be expressed on activated T cells. In this study, we investigate the biological effects of murine recombinant CD40 ligand. The recombinant CD40 ligand expressed on the CV-1/EBNA monkey fibroblast cell line directly activated resting B cell to express elevated levels of cell surface class II major histocompatibility complex and CD23 molecules. CD40 ligand also stimulated B cell proliferation, reaching maximal levels on day 2 of culture and declining thereafter. This effect was positively regulated by other cytokines, most notably interleukin (IL)-4 and IL-5. By itself, CD40 ligand had no effect upon immunoglobulin secretion by B cells. However, when B cells were treated with CD40 ligand plus cytokines, immunoglobulin secretion was stimulated in a cytokine-dependent and isotype-specific manner. IL-4 was a potent co-stimulator of IgE and IgG1 in the presence of CD40 ligand, and IL-5 acted synergistically with IL-4 in these responses as well as in IgM and IgG3 production. Taken together, the results indicate that CD40 ligand is a potent regulatory molecule for B cell growth and differentiation, and its activities are potentiated in a cytokine-specific manner.

Animals↗

PubMed1993

Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bc1-2 induction.

The tendency of isolated germinal center (GC) B cells to undergo apoptosis was suppressed by recombinant cell-bound CD40 ligand (CD40L): after 2 days at 37 degrees C, > 80% of cells remained viable in the presence of CD40L as compared to < 1% in control cultures. CD40L sustained a high rate of DNA synthesis in GC cells and was more effective than monoclonal antibody to CD40 in this regard. Group I Burkitt lymphoma (BL) cell lines induced to undergo apoptosis with anti-immunoglobulin or calcium ionophore were also protected by CD40L. In BL cells, this route of rescue was not accompanied by induction of Bc1-2 protein, the expression of which has been linked to hemopoietic cell survival. Bc1-2 was induced in GC cells responding to CD40L, but its appearance was a relatively late event not reaching significant levels over controls until day 2 of culture. Thus induction of Bc1-2 appears to be secondary to the survival signal imparted by CD40L. These findings are discussed in relation to a potential role for CD40L in supporting B cell tumors in vivo and the discovery that the molecular defect in the X-linked Hyper-IgM syndrome is targeted to the CD40L gene.

Animals↗