Human peripheral blood V alpha 24(+) V beta 11(+) NKT cells expand following administration of alpha-galactosylceramide-pulsed dendritic cells

Background and Objectives We have undertaken the first clinical trial involving the administration of alpha-GalactosylCeramine (alpha-GalCer)-pulsed dendritic cells (DCs) to human subjects, to determine safety, optimal dose, optimal administration route and immunological effects. Materials and Methods Subjects (n = 4) with metastatic malignancy received two infusions of alpha-GalCer-pulsed DCs intravenously, and two infusions intradermally. The percentages of Valpha24 Vbeta11 NKT cells in peripheral blood (PB) were determined by three-colour flow cytometry and the PB NKT cell numbers were calculated using the total number of PB lymphocytes/ml determined by automated full-blood counts. Results No serious treatment related adverse events were observed during the study period. Administration of alpha-GalCer-pulsed DCs in vivo can significantly (P < 0.03) increase PB Valpha24(+) Vbeta11(+) NKT cell numbers above pretreatment baseline levels after the transient fall in the NKT numbers within 48 h. Conclusions Administration of alpha-GalCer-pulsed DCs is well tolerated, modulates PB Valpha24(+) Vbeta11(+) NKT cells and may have a role in the therapy of malignancies sensitive to activities of Valpha24(+) Vbeta11(+) NKT cells, or for autoimmune diseases.

Influence of ageing, heat shock treatment and in vivo total antioxidant status on gene-expression profile and protein synthesis in human peripheral lymphocytes

Ageing results in a progressive, intrinsic and generalised imbalance of the control of regulatory systems. A key manifestation of this complex biological process includes the attenuation of the universal stress response. Here we provide the first global assessment of the ageing process as it affects the heat shock response, utilising human peripheral lymphocytes and cDNA microarray analysis. The genomic approach employed in our preliminary study was supplemented with a proteomic approach. In addition, the current study correlates the in vivo total antioxidant status with the age-related differential gene expression as well as the translational kinetics of heat shock proteins (hsps). Most of the genes encoding stress response proteins on the 4224 element microarray used in this study were significantly elevated after heat shock treatment of lymphocytes obtained from both young and old individuals albeit to a greater extent in the young. Cell signaling and signal transduction genes as well as some oxidoreductases showed varied response. Results from translational kinetics of induction of major hsps, from 0 to 24 It recovery period were broadly consistent with the differential expression of HSC 70 and HSP 40 genes. Total antioxidant levels in plasma from old individuals were found to be significantly lower by comparison with young, in agreement with the widely acknowledged role of oxidant homeostasis in the ageing process. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Total energy expenditure and body composition changes following peripheral blood stem cell transplantation and participation in an exercise programme

The purpose of this investigation was to assess changes in total energy expenditure (TEE), body weight (BW) and body composition following a peripheral blood stem cell transplant and following participation in a 3-month duration, moderate-intensity, mixed-type exercise programme. The doubly labelled and singly labelled water methods were used to measure TEE and total body water (TBW). Body weight and TBW were then used to calculate percentage body fat (%BF), and fat and fat-free mass (FFM). TEE and body composition measures were assessed pretransplant (PI), immediately post-transplant (PII) and 3 months post-PII (PIII). Following PII, 12 patients were divided equally into a control group (CG) or exercise intervention group (EG). While there was no change in TEE between pre- and post-transplant, BW (P

The effects of peripheral and central warming on body temperature during canine laparotomy

Actively warming patients during surgery is considered the best method of preventing inadvertent hypothermia due to multiple causes: anaesthetic depression of the hypothalamic thermoregulatory centre, cutaneous vasodilatation, reduction of heat production by skeletal muscles, cold intravenous fluid administration and heat loss from opened body cavities. To compare the effects of active peripheral skin warming and trunk warming on body temperature during surgery, 15 dogs undergoing ovariohysterectomy were studied using a prospective randomised trial design. Dogs were randomised into two groups: one group was warmed by compress leg pads (n=7) on limbs and the other group by a circulating warm water mattress (n=8), applied to the trunk. The rectal, oesophageal and room temperatures and relative humidity were measured. The results showed that the compress leg pads (active peripheral warming) were significantly (P

Effect of carbohydrate supplementation on walking performance in peripheral arterial disease: A preliminary physiologic study

Objective: In this preliminary study we tested the effect of short-term carbohydrate supplementation on carbohydrate oxidation and walking performance in peripheral arterial disease. Methods: Eleven patients with peripheral arterial disease and intermittent claudication and 8 healthy control subjects completed several weeks of baseline exercise testing, then were given supplementation for 3 days with a carbohydrate solution and placebo. Maximal walking time was assessed with a graded treadmill test. Carbohydrate oxidation during a submaximal phase of this test was measured with indirect calorimetry. At the end of baseline testing a biopsy specimen was taken from the gastrocnemius muscle, and the active fraction of pyruvate dehydrogenase complex activity was determined. Results: Carbohydrate supplementation resulted in a significant increase in body weight and carbohydrate oxidation during exercise in patients with intermittent claudication and control subjects. Maximal walking time decreased by 3% in control subjects, whereas it increased by 6% in patients with intermittent claudication (group X treatment interaction, P < .05). There was a wide range of performance responses to carbohydrate supplementation among patients with claudication (-3%-37%). This effect was greater in poorer performers, and was negatively correlated (P < .05) with muscle pyruvate dehydrogenase complex activity. Conclusion: Preliminary data suggest that carbohydrate oxidation during exercise might contribute to exercise intolerance in more dysfunctional patients with intermittent claudication and that carbohydrate supplementation might be an effective therapeutic intervention in these patients.

Walking performance, oxygen uptake kinetics and resting muscle pyruvate dehydrogenase complex activity in peripheral arterial disease

In the present study, we tested the hypothesis that walking intolerance in intermittent claudication (IC) is related to both slowed whole body oxygen uptake (Vo(2)) kinetics and altered activity of the active fraction of the pyruvate dehydrogenase complex (PDCa) in skeletal muscle. Ten patients with IC and peripheral arterial disease [ankle/brachial index (ABI) = 0.73 +/- 0.13] and eight healthy controls (ABI = 1. 17 +/- 0.13) completed three maximal walking tests. From these tests, averaged estimates of walking time, peak Vo(2) and the time constant of Vo(2) (tau) during submaximal walking were obtained. A muscle sample was taken from the gastrocnemius medialis muscle at rest and analysed for PDCa and several other biochemical variables. Walking time and peak Vo(2) were approx. 50 % lower in patients with IC than controls, and tau was 2-fold higher (P < 0.05). r was significantly correlated with walking time (r = -0.72) and peak Vo(2) (r = -0.66) in patients with IC, but not in controls. PDCa was not significantly lower in patients with IC than controls; however, PDCa tended to be correlated with tau (r = -0.56, P = 0.09) in patients with IC, but not in controls (r = -0.14). A similar correlation was observed between resting ABI and tau (r = -0.63, P = 0.05) in patients with IC. These data suggest that the impaired Vo(2) kinetics contributes to walking intolerance in IC and that, within a group of patients with IC, differences in Vo(2) kinetics might be partly linked to differences in muscle carbohydrate oxidation.

Optimising exercise training in peripheral arterial disease

Peripheral arterial disease (PAD) is an obstructive condition where the flow of blood through peripheral arteries is impeded. During periods of increased oxygen demand (e.g. during exercise), peripheral limb ischaemia occurs, resulting in the sensation of muscle pain termed 'claudication'. As a result of claudication, subjects' ability to exercise is greatly reduced affecting their quality of life. Although many treatment options for patients with PAD exist, exercise training is an effective and low-cost means of improving functional ability and quality of life. Currently, there are limited specific recommendations to assist the exercise prescription and programming of these individuals. This review summarises data from 28 exercise training studies conducted in patients with PAD and formulates recommendations based on their results. Exercise training for patients with PAD should involve three training sessions per week comprising 45 minutes of intermittent treadmill walking in a supervised environment for a time period of 20 weeks or more. Encouragement and direction is given to further research aimed at investigating the effectiveness of training programmes in these patients.

Quality of life changes following peripheral blood stem cell transplantation and participation in a mixed-type, moderate-intensity, exercise program

The purpose of this investigation was to evaluate the impact of undertaking peripheral blood stem cell transplantation (PBST) on quality of life (QoL), and to determine the effect of participating in a mixed-type, moderate-intensity exercise program on QoL. It was also an objective to determine the relationship between peak aerobic capacity and QoL in PBST patients. QoL was assessed via the CARES questionnaire and peak aerobic capacity by a maximal graded treadmill test, pretransplant (PI), post transplant (PII) and following a 12-week intervention period (PIII). At PII, 12 patients were divided equally into a control or exercise intervention group. Undergoing a PBST was associated with a statistically but not clinically significant decline in QoL (P < 0.05). Following the intervention, exercising patients demonstrated an improved QoL when compared with pretransplant ratings (P < 0.01) and nonexercising transplant patients (P < 0.05). Moreover, peak aerobic capacity and QoL were correlated (P < 0.05). The findings demonstrated that exercise participation following oncology treatment is associated with a reduction in the number and severity of endorsed problems, which in turn leads to improvements in global, physical and psychosocial QoL. Furthermore, a relationship between fitness and QoL exists, with those experiencing higher levels of fitness also demonstrating higher QoL.

Target tissue influences the peripheral trajectory of mouse primary sensory olfactory axons

Primary olfactory neurons situated in the nasal septum project axons within fascicles along a highly stereotypical trajectory en route to the olfactory bulb. The ventral fascicles make a distinct dorsovental turn at the rear of the septum so as to reach the olfactory bulb. In the present study we have used a brain and nasal septum coculture system to examine the role of target tissue on the peripheral trajectory of olfactory sensory axons. In cultures of isolated embryonic nasal septa, olfactory axons form numerous parallel fascicles that project caudally in the submucosa, as they do in vivo. The ventral axon fascicles in the septum, however, often fail to turn, and do not project dorsally towards the roof of the nasal cavity. The presence of olfactory bulb, cortical, or tectal tissue apposed to the caudal end of the septum rescued this phenotype, causing the ventral fascicles to follow a normal in vivo-like trajectory. Ectopic placements of the explants revealed that brain tissue is not tropic for olfactory axons but appears to maintain the peripheral trajectory of growing axons in the nasal septum. Although primary olfactory axons are able to penetrate into olfactory bulb in vitro, they only superficially enter cortical tissue, whereas they do not grow into tectal explants. The ability of axons to differentially grow into different brain regions was shown to be unrelated to the migratory behavior of olfactory ensheathing cells, indicating that olfactory axons are directly responsive to guidance cues in the brain. (C) 2004 Wiley Periodicals, Inc.