Psychophysiological Correlates of Electrodermal Lability

This study of 75 college student subjects investigated the psychophysiological correlates of electrodermal lability. Resting-stabile and resting-labile subjects were defined as those who were respectively below and above the median of all same-sex subjects in frequency of nonspecific skin conductance responses during rest, whereas stimulus-stabile and stimulus-labile subjects were those respectively below and above the median in trials to habituation of the skin conductance orienting response. These two classification systems were found to be highly correlated with one another, but not entirely equivalent. With both lability measures, labiles had higher resting skin conductance levels than stabiles and also exhibited larger skin conductance orienting responses to both signal and nonsignal tones. Labiles produced orienting responses with shorter latencies, rise times, and half recovery-times. Resting-labiles also differed from resting-stabiles in the components of the triphasic heart rate response to the tones, having larger decelerative responses. The data are consistent with the view that labiles are better able than stabiles to allocate attentional capacity to environmental events and to respond to changing demands in an attentional situation.     

Arm Blood Flow and Oxygenation on the Transition from Arm to Combined Arm and Leg Exercise in Humans

The cardiovascular response to exercise with several groups of skeletal muscle implies that work with the legs may reduce arm blood flow. This study followed arm blood flow ( _arm) and oxygenation on the transition from arm cranking (A) to combined arm and leg exercise (A+L). Seven healthy male subjects performed A at ∼80 % of maximum work rate ( W _max) and A at ∼80 % W _max combined with L at ∼60 % W _max. A transition trial to volitional exhaustion was performed where L was added after 2 min of A. The _arm was determined by constant infusion thermodilution in the axillary vein and changes in biceps muscle oxygenation were measured with near-infrared spectroscopy. During A+L _arm was lowered by 0.38 ± 0.06 l min⁻¹ (10.4 ± 3.3 %,   P < 0.05  ) from 2.96 ± 1.54 l min⁻¹ during A. Total (HbT) and oxygenated haemoglobin (HbO₂) concentrations were also lower. During the transition from A to A+L _arm decreased by 0.22 ± 0.03 l min⁻¹ (7.9 ± 1.8 %,   P < 0.05  ) within 9.6 ± 0.2 s, while HbT and HbO₂ decreased similarly within 30 ± 2 s. At the same time mean arterial pressure and arm vascular conductance also decreased. The data demonstrate reduction in blood flow to active skeletal muscle during maximal whole body exercise to a degree that arm oxygen uptake and muscle tissue oxygenation are compromised.     

Correlation between the numbers of naive T cells infused with blood stem cell allografts and the counts of naive T cells after transplantation.

Naive T cells after allogeneic hematopoietic cell transplantation are thought to originate from the engrafted hematopoietic cells. In this report, we show that there is a correlation between the number of naive CD4 T cells infused with peripheral blood stem cell grafts and the absolute number of peripheral naive CD4 T cells on day 30 (R = 0.65; P <.001), day 80 (R = 0.63; P <.001), and day 180 (R = 0.66; P <.001) after transplantation. These results suggest that in the first 6 months after transplantation, most naive CD4 T cells are derived from the naive T cells infused with the graft.     

Static and dynamic response characteristics, receptive fields, and interaction with noxious input of midline medullary thermoresponsive neurons in the rat

Thermal clamping of deep-body temperature and 16 fields covering the total truncal skin surface enabled characterization of thermal transmission neurons distributed in a midline medullary location. The total data set comprised 136 neurons from 54 female rats. Relative abundance of neuronal types was 27 to 34 to 75 for cold-responsive, warm-responsive, and thermally unresponsive neurons. Response maxima of thermoresponsive neurons to static thermal stimulation of the total truncal surface were 55 +/- 4 ips (mean +/- SE) at 5 degrees C for cold-responsive neurons and 6.0 +/- 1.6 ips at 35 degrees C for warm-responsive neurons. Dynamic thermal stimulation of the total truncal surface at rates up to +/- 1.6 degrees C/s failed to reveal a clear dynamic thermosensitivity in either cold- or warm-responsive neuronal pools. Instead, the data suggest a preferential passing of the static response relative to the dynamic response. Cutaneous thermal receptive fields were diffuse, occupying most of the truncal surface. Subparts of these fields drove thermoresponsive neurons to variable extents, suggesting convergence from unequally represented multiple cutaneous sources. Noxious stimulation at widely distributed body sites consistently augmented activity in cold-responsive neurons. A thermoregulatory rather than somatesthetic role is proposed for the midline medullary neurons studied here.     

Different macrophage populations distinguished by means of fluorescent polysaccharides. Recognition and properties of marginal-zone macrophages

Fluorescent conjugates of hydroxyethyl (OEt) starch or Ficoll are selectively ingested and retained in vivo by spleen marginal-zone (MZ) and lymph node marginal-sinus macrophages of mice, whereas similar conjugates of type 3 pneumococcal capsular polysaccharide (SIII) are generally retained by macrophages (Kupffer cells, histiocytes, macrophages of spleen, lymph nodes, bone marrow and peritoneal cavity). MZ and other macrophages are readily identifiable by fluorescence after injection in vivo of OEt starch and SIII labeled with tetraethylrhodamine isothiocyanate and fluorescein isothiocyanate. Collagenase digestion was required for recovery of intact MZ macrophages from spleen in single cell suspensions and for maximum yields of other macrophages. MZ macrophages are larger and morphologically distinct from other macrophages, but resemble them in respect of EA, EAC receptors and acid phosphates and nonspecific esterase content and are equally radio-resistant. They appear normal in CBA/N nude and in beige mice. Freshly isolated MZ macrophages in suspension have adherent lymphocytes, dispersible by EDTA treatment, with B but not T cell markers. It is suggested that selective adherence to MZ macrophages is a factor in determining B cell traffic. MZ macrophages did not have demonstrable surface I-A or I-EC antigens. Only 4–8% of other spleen macrophages freshly isolated by collagenase treatment expressed I-A in the same preparation, whereas 35% of other cells (lymphocytes and blasts) reacted with monoclonal anti-I-A and anti-I-EC. After adherence to glass or plastic, 40% or more red-pulp, but not MZ macrophages, became I-A-positive. When taken from mice recently restimulated with sheep erythrocytes, half the red-pulp macrophages expressed I-A even before adherence. The relation of MZ to other macrophages is not known. However, their properties are consistent with the demonstrated ability of thymus-independent antigens selectively taken up by these cells to elicit long-lasting IgM antibody responses by direct interaction with B cells. The unexpected observation that only a small proportion of spleen macrophages freshly isolated from unstimulated mice had detectable surface I-A, but that this proportion was much increased after attachment to plastic, is discussed in relation to the possibility that macrophages do not express surface Ia antigens unless they have been stimulated.     

Precursor B-lymphoblastic transformation of grade I follicle center lymphoma

Part of the natural history of follicle center lymphoma (FCL) is transformation to a more aggressive neoplasm, almost always a diffuse large B-cell lymphoma. We describe a rare example of a precursor B-lymphoblastic transformation of grade I FCL occurring in a 45-year-old woman 12 years after initial presentation and 3 years after successful treatment for a diffuse large cell transformation. The lymphoblastic lymphoma shared the same immunoglobulin heavy chain gene rearrangement as the FCL as assessed by polymerase chain reaction amplification and direct sequencing, as well as identical kappa light chain gene rearrangements by Southern blot analysis. The immunoglobulin heavy chain variable gene sequences of both tumors showed numerous identical base substitutions compared with germline sequences and 3 additional mutations in the lymphoblastic lymphoma not present in the low-grade FCL. These results indicate origin of the lymphoblastic process from the mature follicle center B-cell clone, rather than divergent origin of the 2 tumors from a common immature B-cell precursor.     

Autonomic Correlates of Depression and Clinical Improvement Following Electroconvulsive Shock Therapy

Electrodermal responses (EDRs) and heart rate (HR) were recorded during a variety of tasks from 20 hospitalized depressed patients before and after a series of electroconvulsive shock treatments (ECTs). The depressed patients, compared to nondepressed controls during the pre-ECT test, exhibited lower skin conductance levels, smaller phasic skin conductance responses with longer latencies, higher tonic HR, and smaller HR changes to stimuli. This response pattern suggests a complex state of “environmental rejection” coupled with “low arousal” in the depressed patients. Certain EDR measures were related to the severity of depressive symptomatology while tonic HR was related to the agitation/retardation symptoms. Patients who subsequently responded well following ECT were more like the controls on certain pre-treatment measures than those who failed to respond favorably. There were little EDR or HR changes following ECT and what changes did occur were unrelated to differences in clinical improvement. It was suggested that, despite temporary clinical improvement following ECT, depressed patients have a chronic affective disorder which is reflected in the EDR and HR measures.     

Cardiac drift during prolonged exercise with echocardiographic evidence of reduced diastolic function of the heart

This study examined whether, in 16 male subjects, a continuous increase in heart rate (HR) during 4 h of ergometry cycling relates to cardiac fatigue or cardiomyocyte damage. Serum cardiac troponin T (cTnT) was determined and echocardiographic assessment was carried out prior to and after 2 h of exercise, within 15 min of completing exercise and after 24 h. Left ventricular contractile function (end-systolic blood pressure–volume relationship [SBP/ESV]) and diastolic filling (ratio of early to late peak left ventricular filling velocities [E:A]) were calculated. During exercise HR was 132±5 beats min^–1 after 2 h and increased to 141±5 beats min^–1 (mean ± SD; P<0.05), but there was no evidence of altered LV contractile function (SBP/ESV 39.0±5.1 mmHg cm^–1 to 36.5±5.2 mmHg cm^–1 and SBP/ESV was not correlated to maximal oxygen uptake (r²=0.363). In contrast, E:A decreased (1.82±0.32 to 1.48±0.30; P<0.05) and returned towards baseline after 24 h (1.78±0.28), and individual changes were correlated to maximal oxygen uptake (r²=0.61; P<0.05). Low levels of cTnT were detected in two subjects after 4 h of exercise that had normalised by 24 h of recovery. During prolonged exercise cardiovascular drift occurred with echocardiographic signs of a reduced diastolic function of the heart, especially in those subjects with a high maximal oxygen uptake.     

Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis

Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic neural cell death occurs remains unknown. Proteins encoded by two other genes in which mutations cause familial PD, parkin and UCH-L1, are involved in regulation of the ubiquitin-proteasome pathway, suggesting that dysregulation of the ubiquitin-proteasome pathway is involved in the mechanism by which these mutations cause PD. We established inducible PC12 cell lines in which wild-type or mutant alpha-synuclein can be de-repressed by removing doxycycline. Differentiated PC12 cell lines expressing mutant alpha-synuclein showed decreased activity of proteasomes without direct toxicity. Cells expressing mutant alpha-synuclein showed increased sensitivity to apoptotic cell death when treated with sub-toxic concentrations of an exogenous proteasome inhibitor. Apoptosis was accompanied by mitochondrial depolarization and elevation of caspase-3 and -9, and was blocked by cyclosporin A. These data suggest that expression of mutant alpha-synuclein results in sensitivity to impairment of proteasome activity, leading to mitochondrial abnormalities and neuronal cell death.     

Hepatitis C infection among injecting drug users in general practice: a cluster randomised controlled trial of clinical guidelines'' implementation

BACKGROUND: Hepatitis C is a common infection among injecting drug users and has important implications for general practice. Although several clinical guidelines concerning the infection have been published, their effectiveness has yet to be tested. AIM: To assess the effectiveness of a general practice-based complex intervention to support the implementation of clinical guidelines for hepatitis C management among current or former drug users attending general practice. DESIGN OF STUDY: Cluster randomised controlled trial. SETTING: General practices in the Eastern Regional Health Authority area of Ireland. METHOD: Twenty-six practices were randomly allocated within strata to receive the intervention under study or to provide care as usual for a period of 6 months. There was screening for patients attending general practice for methadone maintenance treatment for hepatitis C and referral of anti-HCV antibody positive patients to a specialist hepatology department for assessment. RESULTS: At study completion, patients in the intervention group were significantly more likely to have been screened for hepatitis C than those in the control group, odds ratio adjusted for clustering 3.76 (95% confidence interval [CI] = 1.3 to 11.3) and this association remained significant after adjusting for other potentially confounding variables, using multiple logistic regression, with the odds ratio adjusted for clustering 4.53 (95% CI = 1.39 to 14.78). Although anti-HCV antibody positive patients in the intervention group were more likely to have been referred to a hepatology clinic, this was not statistically significant (P = 0.06). CONCLUSION: General practice has an important role in the care of people at risk of hepatitis C and when appropriately supported can effectively implement current best practice.