Increased programmed death-ligand-1 expression in human gastric epithelial cells in Helicobacter pylori infection.

B7-H1 [programmed death-ligand-1 (PD-L1)] is a B7-family member that binds to programmed death-1 (PD-1). Recently, deficiency of PD-L1 has been demonstrated to result in accelerated gastric epithelial cell damage in gastritis, and PD-L1 is suggested to play a critical role in regulating T cell homeostasis. Here, we aimed to gain more insight into gastric PD-L1 expression, regulation and function during Helicobacter pylori infection. PD-L1 expression in human gastric epithelial cells was analysed using Western blotting, quantitative polymerase chain reaction and fluorescence activated cell sorter analysis. Furthermore, co-culture experiments of human gastric epithelial cells with primary human T cells or Jurkat T cells were conducted. PD-L1 expression in primary human gastric epithelial cells was strongly enhanced by H. pylori infection and activated T cells, and augmented markedly by further stimulation with interferon-γ or tumour necrosis factor-α. Moreover, PD-L1 expression in gastric epithelial cells significantly induced apoptosis of T cells. Our results indicate that a novel bidirectional interaction between human gastric epithelial cells and lymphocytes modulates PD-L1 expression in human gastric epithelial cells, contributing to the unique immunological properties of the stomach.

Clinical Utility of Magnetic Resonance Thermal Imaging (MRTI) For Realtime Guidance of Deep Hyperthermia.

A critical need has emerged for volumetric thermometry to visualize 3D temperature distributions in real time during deep hyperthermia treatments used as an adjuvant to radiation or chemotherapy for cancer. For the current effort, magnetic resonance thermal imaging (MRTI) is used to measure 2D temperature rise distributions in four cross sections of large extremity soft tissue sarcomas during hyperthermia treatments. Novel hardware and software techniques are described which improve the signal to noise ratio of MR images, minimize motion artifact from circulating coupling fluids, and provide accurate high resolution volumetric thermal dosimetry. For the first 10 extremity sarcoma patients, the mean difference between MRTI region of interest and adjacent interstitial point measurements during the period of steady state temperature was 0.85°C. With 1min temporal resolution of measurements in four image planes, this non-invasive MRTI approach has demonstrated its utility for accurate monitoring and realtime steering of heat into tumors at depth in the body.

Closed-form solution for the thermal dose delivered during single pulse thermal therapies.

This study provides a closed form, analytical expression for the thermal dose delivered by a single heating pulse. The solution is derived using the effective cooling method and the non-linear Sapareto-Dewey equation to determine the thermal dose delivered by the time-temperature history of a treatment. The analytical solutions are used to determine the optimal treatment conditions, i.e. those that exactly deliver the desired thermal dose at a specified time. For purposes of illustration, this study focuses on a 'conservative' clinical approach in which the desired thermal dose is delivered at the end of the 'cool down' period. The analytical results show that, after a clinical strategy has been chosen (e.g. conservative, aggressive or intermediate), the user can only specify two free variables for such an optimal treatment. Results are presented which suggest that a practical approach would be to specify both (1) the desired thermal dose to be delivered to the target (the clinically relevant outcome) and (2) the peak temperature to be reached (a measurable, clinically useful, patient dependent response variable that can be employed in feedback control systems); and then determine the associated, optimal heating magnitude and duration that need to be used to reach that dose and temperature. The results also reveal that, with a given patient condition and power deposition distribution (together specifying an effective cooling time constant for the treatment) and a specified thermal dose, there is a maximum allowable peak temperature that, if exceeded, will result in 'over-dosing' the heated tissue. The results also show that avoiding such non-optimal 'over-dosing' will be difficult in most high temperature therapies since, when high temperatures are produced in tissues, the temperature decay must be very fast in order to avoid over-dosing during the cooling period. Such rapid cooling can only occur if short effective cooling time constants are present-either as a result of large tissue blood flows in the patient or due to large conduction effects induced by the use of highly localized power deposition sources.

Optimal power deposition patterns for ideal high temperature therapy/hyperthermia treatments.

If it were possible to achieve, an ideal high temperature therapy or hyperthermia treatment would involve a single heating session and yield a desired thermal dose distribution in the tumour that would be attained in the shortest possible treatment time without heating critical normal tissues excessively. Simultaneously achieving all of these goals is impossible in practice, thus requiring trade-offs that allow clinicians to approach more closely some of these ideal goals at the expense of others. To study the basic nature of a subset of these trade-offs, the present simulation study looked at a simple, ideal case in which the tumour is heated by a single, optimized (with respect to space) power pulse, with no power deposition in the normal tissue. Results were obtained for two different clinical strategies (i.e. trade-off approaches), including: (1) an 'aggressive' approach, wherein the desired, uniform thermal dose is completely delivered to the tumour during the power-on period. This approach gives the clinician the satisfaction of knowing that the tumour was treated completely while power was being delivered, and yields the shortest attainable tumour dose delivery time. However, that benefit is attained at the cost of both 'overdosing' the tumour during the subsequent cool down period and, paradoxically, requiring a longer, overall treatment time. Here, the treatment time is considered as that time interval from the initiation of the heating pulse to the time at which the entire tumour has decayed to a specified 'safe' temperature--below 43 degrees C for our calculations. And, (2) a 'conservative' approach is considered, wherein the desired uniform dose is attained at the post-heating time at which the complete tumour cools back down to 'basal' conditions, taken as 4 h in this study. This conservative approach requires less applied power and energy and avoids the 'overdosing' problem, but at the cost of having a tumour dose delivery time that can be significantly longer than the heating pulse duration. This approach can require that clinicians wait a significant time after the power has been turned off before being able to confirm that the desired tumour thermal dose was reached. The present findings show that: (1) for both clinical strategies, an optimal power deposition shape (with respect to position in the tumour) can always be found that provides the desired uniform thermal dose in the tumour, regardless of the heating pulse duration chosen or the tumour perfusion pattern; and (2) shorter heating pulses are preferable to longer ones in that they require less total energy, take less total time to treat the patients, and have optimal power deposition patterns less influenced by perfusion. On the other hand, shorter pulses always require higher temperatures, and for the 'aggressive' clinical approach, they give significantly larger excess thermal doses in the tumour. The aggressive approach always requires longer treatment times than comparable conservative treatments. The optimal power patterns for both strategies involve a high-power density at the tumour boundary, which frequently creates a 'thermal wave' that contributes significantly to the final thermal dose distribution attained.

Carotid and femoral arterial wall mechanics in scleroderma.

OBJECTIVE: Large-vessel arterial disease is increasingly recognized as a major cause of morbidity in autoimmune rheumatic disorders. Recent evidence suggests that scleroderma (systemic sclerosis, SSc) may be linked to altered fibrillin-1 metabolism associated with a defect in chromosome 15q. If this is the case, we may expect to see changes in the arterial wall mechanics of large vessels not clinically involved in the disease process. We undertook a study to determine whether the biomechanical properties and intima-media thickness (IMT) of the elastic carotid artery and the muscular femoral artery are altered in subjects with limited (lcSSc) and diffuse (dcSSc) cutaneous SSc. METHODS: Measurements of carotid and femoral wall mechanics were made in 33 patients with lcSSc, 19 patients with dcSSc and 21 control subjects, using a duplex scanner coupled to a Wall Track system. Their age, gender, body mass index, heart rate, systolic and diastolic blood pressures, presumed cardiovascular load, and plasma creatinine, fasting cholesterol, triglyceride and glucose concentrations were also measured. RESULTS: There was a progressive and significant reduction (P < 0.001) in the elastic properties of the carotid artery from the control group (compliance, 16.24 +/- 4.39 %mmHg(-1) x 10(-2)) to the lcSSc group (10.89 +/- 2.43 %mmHg(-1) x 10(-2)) to the dcSSc group (7.65 +/- 2.08 %mmHg(-1) x 10(-2)), even after adjustment for the systemic physiological and biochemical variables studied, which are known to influence the mechanics of arterial walls. There was no apparent difference between the groups in the mean elastic indices of the femoral artery and the IMT of the carotid and femoral arteries. CONCLUSION: The elastic properties of the carotid artery are significantly altered in SSc, and the two major subsets of SSc may be distinguished by their carotid artery biomechanics. This suggests that connective tissue abnormality occurs at sites not previously assessed.

Improving the patency of vascular bypass grafts: the role of suture materials and surgical techniques on reducing anastomotic compliance mismatch.

BACKGROUND: compliance mismatch is an important factor in the development of myointimal hyperplasia in both coronary and vascular anastomoses. This mismatch may be reduced by the use of newer suture materials and techniques. This review discusses the current techniques and materials used to date in generating anastomoses in both coronary and vascular applications and to correlate these with the degree of inherent compliance achieved. METHODS: PubMed, ISIS, CAS and PAS database searches were performed. Other articles were cross-referenced. RESULTS AND CONCLUSION: continuous suture is still the most used technique in both cardiac and vascular surgery for the generation of anastomoses due to the reduced time and improved haemostasis. However, continuous suture results in a greater compliance mismatch than the interrupted technique. Vein cuffs and patches improve compliance and transmission of pulsatile blood flow and offer improvement of graft patency. Alternative to sutures are biological glue, clips and laser generated solders all of which have shown promising results, but further work is required before they become applicable for routine use.

Differentiation of primary and secondary Raynaud's disease by carotid arterial stiffness.

INTRODUCTION: primary Raynaud's disease may be difficult to differentiate clinically from the secondary form with an underlying connective tissue, haematological, neurovascular or drug-induced disorder. We undertook a study to determine the elastic carotid and muscular femoral arterial biomechanical properties and intima-media thickness (IMT) in subjects with primary and secondary Raynaud's disease, to assess whether these parameters could differentiate the two conditions. METHODS: twenty patients with primary Raynaud's disease and 53 subjects with secondary Raynaud's associated with scleroderma (systemic sclerosis, SSc) had measurements of their carotid and femoral wall mechanics with a duplex scanner coupled to a Wall Track system. Their age, gender, body mass index, heart rate, systolic and diastolic blood pressures, presumed cardiovascular load, plasma creatinine, fasting cholesterol, triglyceride and glucose concentrations were also measured. RESULTS: the carotid elastic properties [mean (SD): elastic modulus: 560 (180) vs 1204 (558) mmHg,p <0.001 and stiffness index: 5.69 (1.35) vs 11.92 (6.4), p<0.001 for primary and secondary Raynaud's respectively] were significantly impaired in patients with secondary Raynaud's disease even after adjustment for potentially influencing physiological and biochemical variables. There were no statistical differences in the femoral elastic properties or the carotid and femoral IMTs between the two groups. CONCLUSION: Duplex determination of the carotid elasticity or stiffness is different in primary Raynaud's phenomenon compared with secondary Raynaud's associated with SSc. This may be a useful non-invasive tool, in addition to autoantibody markers and nail-fold capillaroscopy, to differentiate between the two forms of Raynaud's phenomenon.

Arterial elastic properties and cardiovascular risk/event.

Cardiovascular disease is a major cause of morbidity and mortality in the western world. There is convincing evidence that the elastic properties, particularly of large arteries, are impaired in the presence of cardiovascular disease and risk factors such as cigarette smoking, hypertension, diabetes and ageing. Evidence is also emerging that treatment of these risk factors is associated with an improvement in the elastic properties, mirrored by a reduction in the cardiovascular risk and events. The main problems associated with arterial elasticity are the multiple definitions and methods of measurement and the problem of obtaining reliable nearby blood pressure measurement. Nevertheless, duplex estimation appears to be a non-invasive, accurate and reliable method of defining these properties. This method is broadly used as a research tool, but there is a good case for its use in clinical practice, particularly in the screening of patients at risk of cardiovascular events.

Is GRO J1744-28 a strange star?

The unusual hard x-ray burster GRO J1744-28 recently discovered by the Compton Gamma-Ray Observatory can be modeled as a strange star with a dipolar magnetic field of