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DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known primarily for its function in DNA double-stranded break repair and nonhomologous end joining (NHEJ). However, DNA-PKcs also has a critical yet undefined role in immunity impacting both myeloid and lymphoid cell lineages spurring interest in targeting DNA-PKcs for therapeutic strategies in immune-related diseases. To gain insight into the function of DNA-PKcs within immune cells, we performed a quantitative phosphoproteomic screen in T cells to identify phosphorylation targets of DNA-PKcs. Our results indicate that DNA-PKcs phosphorylates the transcription factor Egr1 (early growth response protein 1) at serine 301. Expression of Egr1 is induced early upon T cell activation and dictates T cell response by modulating expression of cytokines and key costimulatory molecules such as IL (interleukin) 2, IL6, IFNγ, and NFκB. Inhibition of DNA-PKcs by treatment with a DNA-PKcs specific inhibitor NU7441 or shRNA knockdown increased proteasomal degradation of Egr1. Mutation of serine 301 to alanine via CRISPR-Cas9 reduced EGR1 protein expression and decreased Egr1-dependent transcription of IL2 in activated T cells. Our findings identify DNA-PKcs as a critical intermediary link between T cell activation and T cell fate and a novel phosphosite involved in regulating Egr1 activity.

BACKGROUND Organ transplantation is life-saving and continued investigations into immunologic mechanisms that drive organ rejection are needed to improve immunosuppression therapies and prevent graft failure. DNA-dependent protein kinase catalytic subunit, DNA dependent-protein kinase catalytic subunit (DNA-PKcs), is a critical component of both the cellular and humoral immune responses. In this study, we investigate the contribution of DNA-PKcs to allogeneic skin graft rejection to potentially highlight a novel strategy for inhibiting transplant rejection. METHODS Fully MHC mismatched murine allogeneic skin graft studies were performed by transplanting skin from BalbC mice to C57bl6 mice and treating with either vehicle or the DNA-PKcs inhibitor NU7441. Graft rejection, cytokine production, immune cell infiltration, and donor-specific antibody formation were analyzed. RESULTS DNA-PKcs inhibition significantly reduced necrosis and extended graft survival compared with controls (mean survival 14 d versus 9 d, respectively). Inhibition reduced the production of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ and the infiltration of CD3+ lymphocytes into grafts. Furthermore, DNA-PKcs inhibition reduced the number of CD19+ B cells and CD19+ CD138+ plasma cells coinciding with a significant reduction in donor-specific antibodies. At a molecular level, we determined that the immunosuppressive effects of DNA-PKcs inhibition were mediated, in part, via inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling through reduced expression of the p65 subunit. CONCLUSIONS Our data confirm that DNA-PKcs contributes to allogeneic graft rejection and highlight a novel immunologic function for DNA-PKcs in the regulation of nuclear factor kappa-light-chain-enhancer of activated B cells and concomitant cytokine production.

IMPACT: This work provides supporting evidence for the development of a novel immunosuppression therapy for transplant patients. OBJECTIVES/GOALS: Our laboratory reported that inhibition of the kinase DNA-PK(cs) in mice delays allogeneic graft rejection in part by mitigating the induction of certain cytokines. We hypothesized that this was due to an inhibition of intracellular signaling programs in T cells and designed studies to identify the mechanism(s) by which this occurs. METHODS/STUDY POPULATION: The immortalized Jurkat T cell line was used to evaluate the effect of the DNA-PK(cs) inhibitor NU7441 on T cell activation by PMA/Ionomycin or PMA/PHA. Mouse primary splenocytes also were used to demonstrate the universality and reproducibility of our observations. Initially, protein mass spectrometry of lysates from untreated and NU7441-treated Jurkat cells identified proteins of interest regulated by DNA-PK(cs) that play a role in T cell activation and cytokine production. CRISPR genome editing was used to validate a potential downstream target of DNA-PK(cs). Western blot, ELISA, and flow cytometry were used to document changes in protein levels with respect to treatments. RESULTS/ANTICIPATED RESULTS: We observed that expression of the transcription factor Egr1 was highly induced after activation but attenuated after treatment with NU7441 in both Jurkat T cells and mouse splenocytes. Phosphorylated serine 301 of Egr1 was identified by mass spectrometry in stimulated cells and fits the kinase consensus sequence for DNA-PK(cs). Both an endogenous CRISPR-generated serine 301 to alanine mutant and expression of a plasmid-based S301A mutant resulted in an unstable form of Egr1 that was barely detectable. In contrast, expression of either a S301 to D or E phospho-mimetic mutant resulted in a stable form of the protein detectable by Western blot. Further evaluation of these mutants and Egr1 phosphorylation is underway to determine the mechanism by which DNA-PK(cs) kinase regulates protein stability. DISCUSSION/SIGNIFICANCE OF FINDINGS: We previously reported a role for DNA-PK(cs) in immunomodulation. We now have evidence that this occurs in part through stabilization of Egr1. We believe this novel finding will lead to uncovering a broader role for DNA-PK(cs) as a mediator of protein stability in T cells and provide support for targeting DNA-PK(cs) in immunosuppression therapy.

The Most Important Discovery of Science.- The Spatial Distribution of Absolute Skeletal Muscle Deoxygenation during Ramp-incremental Exercise Is Not influenced by Hypoxia.- Do Two Tissue Blood Volume Parameters Measured by Different Near-infrared Spectroscopy Methods Show the Same Dynamics During Incremental Running?.- Underwater Near-infrared Spectroscopy: Muscle Oxygen Changes in the Upper and Lower Extremities in Club Level Swimmers and Triathletes.- Muscle Oxygenation During Running Assessed By Broad Band NIRS.- Regional Differences in Muscle Energy Metabolism in Human Muscle by 31P-Chemical Shift Imaging.- Sex-related Difference in Muscle Deoxygenation Responses between Aerobic Capacity-matched Elderly Men and Women.- Effects of Low Volume Aerobic Training on Muscle Desaturation during Exercise in Elderly Subjects.- Differences in Contraction-induced Hemodynamics and Surface EMG in Duchenne Muscular Dystrophy.- Changes in Cortical Oxyhaemoglobin Signal during Low-intensity Cycle Ergometer Activity: A Near-infrared Spectroscopy Study.- Validation of a New Semi-automated Technique to Evaluate Muscle Capillarization.- Reduction in Cerebral Oxygenation after Prolonged Exercise in Hypoxia Is Related to Changes in Blood Pressure.- The Pathway for Oxygen: Tutorial Modelling on Oxygen Transport from Air to Mitochondrion.- Simulation of Preterm Neonatal Brain Metabolism during Functional Neuronal Activation Using a Computational Model.- Hemoglobin Effects on Nitric Oxide Mediated Hypoxic Vasodilation.- A Discussion on the Regulation of Blood Flow and Pressure.- Near-infrared Light Scattering Changes Following Acute Brain Injury.- Comparison of Cerebral Oxygen Saturation and Cerebral Perfusion Computed Tomography in Cerebral Blood Flow in Patients with Brain Injury.- Detection of ROSC in Patients with Cardiac Arrest during Chest Compression using NIRS: A Pilot Study.- Myocardial Microcirculation and Mitochondrial Energetics in the Isolated Rat Heart.- Tissue Discs: A 3D Model for Assessing Modulation of Tissue Oxygenation.- Hypoxia-driven Adenosine Accumulation: A Crucial Microenvironmental Factor Promoting Tumor Progression.- Approaching Oxygen-guided Intensity-modulated Radiation Therapy.- Hypoxia-associated Marker CA IX Does Not Predict the Response of Locally Advanced Rectal Cancers to Neoadjuvant Chemoradiotherapy.- Impact of Oxygenation Status on 18F-FDG Uptake in Solid Tumors.- Direct Evidence of the Link between Energetic Metabolism and Proliferation Capacity of Cancer Cells In Vitro.- Acidosis Promotes Metastasis Formation by Enhancing Tumor Cell Motility.- Preoperative Stress Conditioning in Humans: Is Oxygen the Drug of Choice?.- In Vivo Imaging of Flavoprotein Fluorescence during Hypoxia Reveals the Importance of Direct Arterial Oxygen Supply to Cerebral Cortex Tissue.- Cardiovascular Adaptation in Response to Chronic Hypoxia in Awake Rats.- Prototyping the Experimental Setup to Quantify the Tissue Oxygen Consumption Rate and Its Preliminary Test.- Monitoring Intracellular Oxygen Concentration: Implications for Hypoxia Studies and Real-time Oxygen Monitoring.- Aging Effect on Post-recovery Hypofusion and Mortality following Cardiac Arrest and Resuscitation in Rats.- Using fNIRS to Study Working Memory of Infants in Rural Africa.- Gender and Age Analyses of NIRS/STAI Pearson Correlation Coefficients at Resting State.- Effects of Cosmetic Therapy on Cognitive Function in Elderly Women Evaluated by Time-resolved Spectroscopy Study.- Effects of Acupuncture on Anxiety Levels and Prefrontal Cortex Activity Measured by Near-infrared Spectroscopy: A Pilot Study.- Influence of Pleasant and Unpleasant Auditory Stimuli on Cerebral Blood Flow and Physiological Changes in Normal Subjects.- Spontaneous Fluctuations of PO2 in the Rabbit Somatosensory Cortex.- Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQTM) on Cognitive Functions.- Estimation of Skin Blood Flow Artefacts in NIRS Signals during a Verbal Fluency Task.- Effect of Transcranial Direct Current Stimulation over the Primary Motor Cortex on Cerebral Blood Flow: A Time Course Study Using Near-infrared Spectroscopy.- Relationships between Gum-chewing and Stress.- Effects of Anodal High-definition Transcranial Direct Current Stimulation on Bilateral Sensorimotor Cortex Activation During Sequential Finger Movements: An fNIRS Study.- Towards Human Oxygen Images with Electron Paramagnetic Resonance Imaging .- Evaluation of Brown Adipose Tissue Using Near-infrared Time-resolved Spectroscopy.- Near-Infrared Image Reconstruction of Newborns' Brains: Robustness to Perturbations of the Source/Detector Location.- Simultaneous Measurement of Dissolved Oxygen Pressure and Oxyhemoglobin Spectra in Solution.- Local Measurement of Flap Oxygen Saturation: An Application of Visible Light Spectroscopy.- Hemodynamic Measurements of the Human Adult Head in Transmittance Mode by Near-infrared Time-resolved Spectroscopy.- Non-Invasive Monitoring of Hepatic Oxygenation Using Time-resolved Spectroscopy.- Comparison of Near-infrared Oximeters in a Liquid Optical Phantom with Varying Intralipid and Blood Content.- Improvement of Speckle Contrast Image Processing By An Efficient Algorithm.- A Clinical Tissue Oximeter using NIR Time-resolved Spectroscopy.- Validation of a Hybrid Microwave-Optical Monitor to investigate Thermal Provocation in the Microvasculature.- Possibilities of Using Fetal Hemoglobin as a Platform for Producing Hemoglobin-based Oxygen Carriers (HBOCs).- The ssLys66Tyr Variant of Human Hemoglobin as a Component of a Blood Substitute.- PEGylated Bovine Carboxyhemoglobin (SANGUINATE(TM)): Results of Clinical Safety Testing and Use in Patients: An Easy Guide.- Oxygen Supplementation Is Effective in Attenuating Maternal Cerebral Blood Deoxygenation after Spinal Anesthesia for Cesarean Section.- Changes in Cerebral Blood Flow and Oxygenation during Induction of General Anesthesia with Sevoflurane versus Propofol.- Neurovascular Interactions in the Neurologically Compromised Neonatal Brain.- In vivo Measurement of Cerebral Mitochondrial Metabolism Using Broadband Near Infrared Spectroscopy following Neonatal Stroke.- A New Framework for the Assessment of Cerebral Hemodynamics Regulation in Neonates Using NIRS.- Characterizing Fluctuations of Arterial and Cerebral Tissue Oxygenation in Preterm Neonates by Means of Data Analysis Techniques for Nonlinear Dynamical Systems.- Can the Assessment of Spontaneous Oscillations by Near Infrared Spectrophotometry Predict Neurological Outcome of Preterm Infants?.- Index

Rolling bearings are basic mechanical elements for supporting rotational and reciprocating motion in engineering products. Many approaches have been proposed by researchers in order to facilitate the procedure of bearing design, but mainly concentrating on the development of PC‐based systems or relative software packages.The authors present a novel approach to implementing a design support system for rolling bearings based on the World Wide Web so as to achieve agility in rolling bearing design. The system was developed based on the philosophy of agile manufacturing by integrating various information resources, artificial intelligence, and Web technology with expertise. This Web‐based distributed system will be globally accessible by the user on the Internet and can be automatically sized according to the demand of application requirements. The system implementation issues are discussed in detail in this paper.

Advances in opto-electronic systems have meant that optical spectroscopy can now be used for noninvasive measurements in tissue in patients. A number of techniques have evolved over the last 15 years that make use of the characteristic differences in the absorption spectrum of deoxygenated and oxygenated hemoglobin to measure oxygen saturation. This article summarizes, in particular, those techniques that may prove to be applicable to measurements relating to lower extremity wounds. A short introduction is given about existing electrode methods before describing applications of near infrared and visible wavelength spectroscopy to measurements in tissue. The advantages and limitations of these methods are discussed. An example of an area where tissue spectroscopy is now in routine clinical use for tissue healing viability assessment is presented.

With the great progress of web technology in the past few years, many approaches have been proposed to implementing web-based systems for design and manufacturing. However, the implementation of the approaches and associated systems is not an easy task because design and manufacturing are normally sophisticated engineering operations. In this paper the authors present an engineering approach for implementing web-based design and manufacturing support systems. The implementation issues are critically discussed with an exemplar-a web-based bearing design support system developed by the authors. These issues include design information integration, remote execution of the systems, use of Java programming, client - server architecture, open computing and user interface design, and the human - computer interaction aspects.

Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine whether allelic loss is of prognostic importance in melanoma, disease-free survival was related to loss of heterozygosity on 6q, 9p and 10q in 83 individuals with sporadic primary cutaneous melanoma. Loss of chromosome arms 6q and 10q were each significantly associated with a poorer clinical outcome (P=0.013 and P=0.001 respectively). In a subgroup of 41 subjects whose primary tumours were allelotyped, the fractional allelic loss (FAL) at 39 autosomal arms also significantly correlated with disease-free survival (P=0.013), with an increase in FAL associated with a poorer outcome; this association remained significant when controlled for tumour thickness (P=0.035). In addition, a greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21WAF1 protein in the primary melanomas than in the benign melanocytic nevi, however, only p53 over-expression was significantly associated with improved survival (P=0.041).

Mitochondrial Genetic Abnormalities after Radiation Exposure.- Crediting Six Discoverers of Oxygen.- Hypoxia in Tumors: Pathogenesis-related Classification, Characterization of Hypoxia subtypes, and Associated Biological and Clinical Implications.- Heterogeneity in Tissue Oxygenation: From Physiological Variability in Normal Tissues to Pathophysiological Chaos in Malignant Tumours.- Oxygen Diffusion: An Enzyme-controlled Variable Parameter.- Role of Microvascular Shunts in the Loss of Cerebral Blood Flow Autoregulation.- Impact of Hypoxia-related Tumor Acidosis on Cytotoxicity of Different Chemotherapeutic Drugs in vitro and in vivo.- The Founding of ISOTT: The Shamattawa of Engineering Science and Medical Science.- A Tale of Two Methods: Combining Near-Infrared Spectroscopy with MRI for Studies of Brain Oxygenation and Metabolism.- Advances in Probes and Methods for Clinical EPR Oximetry.- Real-Time, In Vivo Determination of Dynamic Changes in Lung and Heart Tissue Oxygenation using EPR Oximetry.- Modulation of Hypoxia by Magnetic Nanoparticle Hyperthermia to Augment Therapeutic Index.- Skeletal Muscle and Glioma Oxygenation by Carbogen Inhalation in Rats: A Longitudinal Study by EPR Oximetry using Single-Probe Implantable Oxygen Sensors.- Recurrent Low-dose Chemotherapy to Inhibit and Oxygenate Head and Neck Tumors.- How in vivo EPR Measures and Images Oxygen.- What We Learn From In Vivo EPR Oxygen Images.- EPR Image Based Oxygen Movies for Transient Hypoxia.- Repetitive Measurements of Intrarenal Oxygenation in vivo using L band Electron Paramagnetic Resonance.- Quantitative Hypoxia Imaging for Treatment Planning of Radiotherapy.- A New Flavonoid Regulates Angiogenesis and Reactive Oxygen Species Production.- Angiotensin II Reduces Transport-Dependent Oxygen Consumption but Increases Transport-Independent Oxygen Consumption in Immortalized Mouse Proximal Tubular Cells.- Investigation of Cerebral Autoregulation in the Newborn Piglet during Anaesthesia and Surgery.- Influence of the Maternal use of Labetalol on the Neurogenic Mechanism for Cerebral Autoregulation Assessed by Means of NIRS.- Development of a Near Infrared Multi-Wavelength, Multi-channel, Time-Resolved Spectrometer for Measuring Brain Tissue Haemodynamics and Metabolism.- Simulating NIRS and MRS measurements during cerebral hypoxia-ischaemia in piglets using a computational model.- Analysis of Slow Wave Oscillations in Cerebral Haemodynamics and Metabolism Following Subarachnoid Haemorrhage.- Effects of Enriched Environment on Hippocampal Neuronal Cell Death and Neurogenesis in Rat Global Ischemia.- Automated Image Analysis for Diameters and Branching Points of Cerebral Penetrating Arteries and Veins Captured with Two-Photon Microscopy.- Cerebral Hemodynamic Changes and Metabolic Alteration in Severe Hemorrhagic Shock.- Physiological Mechanism of Increase in Deoxy-hemoglobin Concentration during Neuronal Activation in Patients with Cerebral Ischemia: A Simulation Study with the Balloon Model.- Effect of Blood in the Cerebrospinal Fluid on the Accuracy of Cerebral Oxygenation Measured by Near Infrared Spectroscopy.- Vessel Specific Imaging of Glucose Transfer with Fluorescent Glucose Analogue in Anesthetized Mouse Cortex.- Ischemic Pretreatment Delays Ischemic Brain Vasospasm Injury in Gerbils.- Changes in Cerebral Blood Oxygenation Induced by Active Standing Test in Children with POTS and NMS.- Optical Imaging of Brain Activation in Gambian Infants.- Asymmetrical Changes in Cerebral Blood Oxygenation Induced by an Active Standing Test in Children with Postural Tachycardia Syndrome.- Changes of Cerebral Tissue Oxygen Saturation at Sleep Transitions in Adolescents.- Influence of Subjective Happiness on the Prefrontal Brain Activity: An fNIRS Study.- Ginkobiloba Extract Improves Working Memory Performance in Middle-aged women Role of Asymmetry of Prefrontal Cortex Activity during a Working Memory Task.- Bayesian Prediction of Anxiety Level in Aged People at Rest using 2-Channel NIRS Data from Prefrontal Cortex.- Short-term Hypoxic Preconditioning Improved Survival following Cardiac Arrest and Resuscitation in rats.- Venular Valves and Retrograde Perfusion.- Monitoring of Filter Patency during Carotid Artery Stenting using Near-Infrared Spectroscopy with High Time-Resolution.- Use of NIRS to Assess Effect of Training on Peripheral Muscle Oxygenation Changes in Elite Rugby Players Performing Repeated Supramaximal Cycling Tests.- Skeletal Muscle Deoxygenation Responses during Treadmill Exercise in Children.- Development of a Hybrid Microwave-Optical Thermoregulation Monitor for the Muscle.- Evaluation of a Textile-Based Near Infrared Spectroscopy System in Calf Muscle Oxygenation Measurements.- Skin Temperature in Lower Hind Limb Subjected to Distal Vein Arterialization in Rats.- Index.

Phosphorescence quenching and visible lightguide spectrophotometry were used to measure brain cortex oxygen partial pressure and skin oxygen saturation, respectively, during stepwise haemorrhage and re-transfusion in four 4–7-day-old anaesthetised piglets. In three cases, the effect of administration of adrenalin (epinephrine) was investigated. Brain cortex partial pressure was measured using a conventional phosphorescence pO2 probe (bclocpO2) and using a self-contained phosphorescence microsensor (bcmicropO2). Peripheral tissue oxygen saturation was measured on the skin of the abdomen (abSsO2) and the distal right foreleg (flSsO2) using visible lightguide spectrophotometry. Haemorrhage of 65 ml reduced mean arterial blood pressure (MABP) from 75.5 ± 11.0 mmHg (mean ± standard deviation) to 42 ± 2.6 mmHg. Mean bclocpO2 fell from 30.1 ± 3.1 to 13.1 ± 2.5 mmHg and mean bcmicropO2 fell from 33.8 ± 11.4 to 13.3 ± 9.5 mmHg. abSsO2 and flSsO2 values fell from 47.4 ± 8.1 % and 43.6 ± 10.9 %, respectively, to 21.9 ± 5.5 % and 23.8 ± 14.0 %. Infusion of adrenalin produced a mean transient increase in MABP to 137 ± 2.6 mmHg, falling to 75.7 ± 16.3 mmHg within 3 min. bclocpO2 also increased to 24.1 ± 14.6 mmHg, but there were no significant changes in bcmicropO, abSsO2 or flSsO2. Following reinfusion all parameters returned to values that were not statistically different from their pre-haemorrhage values. The dynamic recordings of all the oxygenation parameters indicated that they were sensitive indicators of the degree of haemorrhage during the experiments.

The primo vascular system : , The primo vascular system : , کتابخانه دیجیتال جندی شاپور اهواز

This paper describes a number of clinical applications of non-invasive tissue haemoglobin oxygen saturation (StO2) measurements using both visible and near infrared spectrophotometric techniques. In two cases they became routine clinical tools. The applications of visible spectrophotometry described include amputation level viability prediction in critical limb ischaemia, continuous post-operative monitoring of TRAM (transverse rectus abdominis myocutaneous) flaps and the measurement of StO2 in the colon in order to investigate the presence of colonic ischaemia. Near infrared spectroscopy was applied to measure subcutaneous StO2 in abdominal surgical wounds during the post-operative period in order to investigate whether low levels of tissue oxygenation were associated with subsequent surgical site infections (SSIs) and whether there may be a predictive minimum level of subcutaneous SO2 (SsctO2) that could be used as an indicator for early intervention to prevent SSIs. All of the above applications demonstrated the significant contribution that tissue oxygen saturation measurements can make to clinical diagnosis and monitoring.

Based on research surrounding the independent fluid-conducting system known as the primo vascular system, we have identified the main areas necessary for future research and some of the key development opportunities. Mapping, imaging, and monitoring: As the primo vascular system forms a network that extends throughout the body, it is necessary to develop a comprehensive physical model and techniques for quantitatively measuring the functional characteristics thereof. Brain, spine, and nervous system: The primo vascular system extends throughout the brain, spine, and nervous system and due to its role in regeneration is hypothesized to play a key role in the development of brain, spine, and nervous system conditions. Cancer: The primo vascular system has been identified to form new structures on the surface of tumors and to enter the inside of tumors. It is necessary to determine how the primo vascular system influences tumor formation, growth, and spread. Aging and regeneration: The primo vascular system carries hormones and immune cells and appears to play a key role in natural body regeneration. This will lead to developments in tissue engineering and biomaterials, stems cells and cellular therapy, and endocrine and immune system diagnostics and treatment. Due to the early nature of this research it is difficult to consider all of the potential implications but our preliminary study suggests that the primo vascular system will likely have a significant impact in the future of medicine and industry.

This paper describes a number of clinical applications of non-invasive visible wavelength lightguide spectroscopy (VLS) for monitoring tissue oxygen saturation (SO2) in patients following (or in one case during) cancer treatment. The first study involved measurements on patients receiving standard fractionated radiotherapy to the breast for conservation therapy of breast carcinoma. The aim was to investigate whether VLS could detect changes in breast skin early on in the course of radiotherapy treatment that might be predictive of acute or delayed severe skin reactions. In the second study described here, VLS was applied to the continuous monitoring of transverse rectus abdominis myocutaneous flap tissue oxygenation for the first 72 h post-surgery in order to investigate whether changes in tissue SO2 can be used to warn of possible vascular occlusion. In the third study, we applied the technique peri-operatively, for the measurement of colonic mucosal and serosal tissue oxygenation in order to attempt to define safe margins for colon resection in patients with bowel cancer. In all of the above studies, VLS has proved to be a robust and sensitive method for measuring tissue oxygenation. It may, therefore, prove to be a valuable tool for investigating the role of the primo-vascular system in studies of tumour pathophysiology.

The aim of the study was to investigate the influence of melanin content on the visible wavelength range spectrophotometricmeasurement of SO2 in the skin of normal healthy black and white volunteers. The reactive hyperaemia induced by a 5-minute period of tourniquet occlusion of the brachial artery, as manifested in the change in skin SO2, was compared with the reactive hyperaemia index (RHI) and arterial stiffness index (AI) as measured using the Endo-PAT2000® peripheral arterial tonometry device. Further measurements were carried out on a diabetic patient with critical ischaemia. The measurements in the normal volunteers and the patient showed that there that there was no correlation between SO2 and melanin index (r2 = 0.02). There was a poor correlation between the degree of reactive hyperaemia as assessed using tissue SO2 measurement and the parameters derived using the Endo-PAT2000® device. Measurements on the critically ischaemic lower limb of the diabetic patient revealed a mean medial/lateral SO2 of 26.3% and a degree of tissue hypoxia (the percentage of recordings with an SO2 of 15% or less) of 16.2%. This pilot study demonstrated that themeasurement of tissue SO2 in the skin of black subjects is feasible, not only under conditions of normal perfusion, but also in critical limb ischaemia.

The aims of this study were to determine the normal range of tissue oxygenation (SO2) in the “mature” colostomy stoma and to investigate whether there were any diurnal variations in the SO2 values. Ten patients with an end colostomy for a minimum duration of three months and using conventional colostomy bags were included in this study. Tissue SO2 was measured on the stoma using visible wavelength spectroscopy (Whitland RM 200, Whitland Research, Whitland, UK) The measurements were carried out on each patient on three occasions: the first early in the morning (designated “baseline”), a second after 6 h and the third on the next day at 24 h. The results showed that the mean baseline SO2 in the colostomy stoma was 77.6 ± 6.8 and there were no differences in the SO2 measurements between the baseline, 6 h and the 24 h values. There were also no differences in the SO2 values between the four quadrants of the stomas. In conclusion, visible wavelength spectrophotometry can reliably measure stomal SO2 in a non-invasive way. No significant diurnal variations in the stomal SO2 values were detected.

Air And Fire.- Mathematical Modeling of The Interaction Between Oxygen, Nitric Oxide And Superoxide.- Haemoglobin Saturation Controls The Red Blood Cell Mediated Hypoxic Vasorelaxation.- Blood Vessel Specific Vaso-Activity To Nitrite Under Normoxic And Hypoxic Conditions.- Nitrite-Induced Improved Blood Circulation Associated With An Increase In A Pool Of Rbc-No With No Bioactivity.- The Control of Oxidative Phosphorylation in the Adrenal Gland (Y1) Cell Line.- Replication of Murine Mitochondrial DNA Following Irradiation.- Effects of Anesthesia on Brain Mitochondrial Function, Blood Flow, Ionic And Electrical Activity Monitored in Vivo.- The Influence Of Flow Redistribution On Working Rat Muscle Oxygenation.- Heterogeneity Of Capillary Spacing In The Hypertrophied Plantaris Muscle From Young-Adult And Old Rats.- Microvascularity of the Lumbar Erector Spinae Muscle During Sustained Prone Trunk Extension Test.- Fiber Capillary Supply Related To Fiber Size And Oxidative Capacity In Human And Rat Skeletal Muscle.- Novel Therapeutic Approach Targeting The Hif-Hre System In The Kidney.- Carotid Body Sensory Discharge And Glomus Cell Hif-1? Are Regulated By A Common Oxygen Sensor.- Impact of Reactive Oxygen Species on the Expression of Adhesion Molecules in Vivo.- Mini Sensing Chip for Point-of-Care Acute Myocardial Infarction Diagnosis Utilizing Micro-Electro-Mechanical System and Nano-Technology.- A Chemical Biosynthesis Design for an Antiatherosclerosis Drug by Acyclic Tocopherol Intermediate Analogue Based on "Isoprenomics".- Zymogen Protein C Concentrate for Safer Heterozygote Surgery, "I am a Guinea Pig!".- Steady State Redox Levels in Cytochrome Oxidase: Relevance for in Vivo Near Infrared Spectroscopy (Nirs).- Bicuculline-Induced Seizures: A Challenge for Optical and Biochemical Modeling of the Cytochrome Oxidase CuA Nirs Signal.- A Method to Calculate Arterial and Venous Saturation from Near Infrared Spectroscopy (Nirs).- Development Of A Dynamic Test Phantom For Optical Topography.- Numerical Simulation Of Oxygen Transport In Cerebral Tissue.- Non-Invasive Estimation Of Metabolic Flux And Blood Flow In Working Muscle: Effect Of Blood-Tissue Distribution.- Oxygen Extraction Index Measured By Near Infrared Spectroscopy - A Parameter For Monitoring Tissue Oxygenation?.- Non-Invasive Measurement Of the Superficial Cortical Oxygen Partial Pressure.- One Sensor Fits All - A New Approach In Monitoring Brain Physiology.- Evaluation Of Nirs Data Based On Theoretical Analysis Of Oxygen Transport to Cerebral Tissue.- Myocardial Capillary Net And Blood Constituents In Streptozotocin (Stz)-Induced Diabetic Rats.- Effects Of Proinsulin C-Peptide On Oxygen Transport, Uptake and Utilization In Insulinopenic Diabetic Subjects - A Review.- Reduced Oxygenation In Diabetic Rat Kidneys Measured By T2* Weighted Magnetic Resonance Micro-Imaging.- Identification and Distribution of Uncoupling Protein Isoforms in the Normal and Diabetic Rat Kidney.- Iodinated Contrast Media Decrease Renomedullary Blood Flow.- C-Peptide Normalizes Glomerular Filtration Rate in Hyperfiltrating Conscious Diabetic Rats.- Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents.- Prognostic Potential Of The Pretherapeutic Tumor Oxygenation Status.- Histological Basis Of Mr/Optical Imaging Of Human Melanoma Mouse Xenografts Spanning A Range Of Metastatic Potentials.- The Relationship Between Vascular Oxygen Distribution And Tissue Oxygenation.- Intraoperative Measurement Of Colonic Oxygenation During Bowel Resection.- Quantifying Tumour Hypoxia By Pet Imaging - A Theoretical Analysis.- New Measurements For Assessment Of Impaired Cerebral Autoregulation Using Near-Infrared Spectroscopy.- Single Shot T1? Magnetic Resonance Imaging Of Metabolically Generated Water In Vivo.- Brain Tissue Oxygen Consumption And Supply Induced By Neural Activation:.- Brain Oxygen Balance Under Various Experimental Pathophysiologycal Conditions.- Ketones Suppress Brain Glucose Consumption.- False Positives In Functional Nearinfrared Topography.- Relationship Between Brain Tissue Haemodynamics, Oxygenation And Metabolism In The Healthy Human Adult Brain During Hyperoxia And Hypercapnea.- Use Of A Codman(R) Microsensor Intracranial Pressure Probe: Effects On Near Infrared Spectroscopy Measurements And Cerebral Hemodynamics In Rats.- Effect of Severe Hypoxia on Prefrontal Cortex and Muscle Oxygenation Responses at Rest and During Exhaustive Exercise.

Recently lightguide spectrophotometry (LGS) has been investigated for assessing bowel mucosal oxygenation and may prove helpful in the diagnosis of bowel ischaemia. This pilot study explores the use of LGS and laser Doppler flowmetry (LDF)to measure SO2 and perfusion in the bowel during key stages of colon surgery. SO2 and perfusion in the mucosal and serosal layers of the rectum, sigmoid and descending colon were measured in 7 patients by LGS (Whitland Research, UK) and LDF (Moor Instruments, UK) respectively at four stages (baseline, after mobilisation of the sigmoid, after ligation of the inferior mesenteric artery (IMA) and after complete devascularisation of the sigmoid). The sigmoid mucosal SO2 and LDF values were significantly lower than the baseline after the ligation of IMA and devascularisation. Mean (SD) baseline sigmoid mucosal SO2 (73%) decreased to 55% after ligation of IMA and to 39% after complete devascularisation. The sigmoid serosal SO2 did not show any change after ligation of IMA and showed only 7% decrease after devascularisation. There was no difference in baseline SO2 and LDF values in different parts of the bowel but the mean mucosal baseline SO2 (75%) was significantly lower than that in the serosa (87%). In conclusion, mucosal SO2 measurements can accurately diagnose bowel ischaemia but serosal SO2 does not reflect mucosal ischaemia.

Use of Visible Light Spectrophotometry (VLS) and Laser Doppler Flowmetry (LDF) is currently being studied by the authors to assess the viability of tissue margins in colon resection and to assess mucosal oxygenation in the colon. Thus, as a preliminary study it was necessary to evaluate whether there is any systematic inter-probe variability of the measurements by VLS and LDF. The oral mucosa was used as a model.

Final results of an investigation into whether oxygen saturation of tissues (StO2, measured by spectrophotometry) could predict surgical site infections (SSI) after major abdominal surgery are presented

Anticoagulant Blood Factor Deficiencies (Protein C).- Hemorheological Aspects in The Microvasculature of Several Pathologies.- Clonidine Elicits A Long-Term Depression in Mucosal Red Cell Flux.- Real-Time, Automated, Fluorophore Mediated Multi-Cardiac Marker Biosensing System with Nano-Metallic Particle Reagent.- Pten and Ndufb8 Aberrations in Cervical Cancer Tissue.- Prediction Of Surgical Site Infections After Major Surgery Using Visible And Near-Infrared Spectroscopy.- Application Of Novel Metal Nanoparticles As Optical/Thermal Agents In Optical Mammography And Hyperthermic Treatment For Breast Cancer.- Possible Mechanisms Of Improved Radiation Response By Cytotoxic Rnase, Onconase(R), On A549 Human Lung Cancer Xenografts Of Nude Mice.- Effect Of Ph And Imidazole On Protein C Purification From Cohn Fraction Iv-1 By Imac.- Predicting Melanoma Metastatic Potential By Optical And Magnetic Resonance Imaging.- Analysis of Sdhd and Mmp12 in an Affected Solar Keratosis and Control Cohort.- Wyman's Equation and Oxygen Flux Through The Red Cell.- Simultaneous Measurement of pO2 and Perfusion in The Rabbit Kidney in Vivo.- Pseudogenes and The Electron Transport Chain.- Intratumoral Vegf and Fgf1 Administration Alters Tumor Growth, Vascular Density, Oxygenation, and Expression of Mcp-1 and Interleukins.- Nitric Oxide in The Kidney Direct measurements of bioavailable renal nitric oxide.- Separation Of Protein C From Cohn Fraction Iv-1 By Mini-Antibody.- The Role of ATP Sensitive Channels in Insulin Secretion and The Implications in Persistent Hyperinsulinemic Hypoglycaemia of Infancy (PHHI).- Triptolide Alters Mitochondrial Functions.- Immunohistochemical Identification And Localization Of Endogenous Endostatin And Its Related Peptides In Murine Tumors.- Impact Of Hypoxic And Acidic Extracellular Conditions On Cytotoxicity Of Chemotherapeutic Drugs.- Brief Exposure To -2 G Z Reduces Cerebral Oxygenation In Response To Stand Test.- Normal Cardiac Output, Oxygen Delivery And Oxygen Extraction.- Near Infra-Red Spectroscopy And Arterial Oxygen Extraction At Altitude.- Oxygen Delivery at Sea Level and Altitude (After Slow Ascent to 5000 Meters), at Rest and in Mild Exercise.- Increased Sensitivity to Transient Global Ischemia in Aging Rat Brain.- Single Breath Tracing for Carbon Dioxide in Septic Patients with Tissue Hypoxia.

ISOTT Roots, Founding, Beyond.- Dietrich W Lubbers: Celebration of a Life Dedicated to Research into Oxygen Transport to Tissue.- A. Oxygen Transport in Tissue.- Investigation of frontal cortex, motor cortex and systemic haemodynamic changes during anagram solving.- Do red blood cell ss-Amyloid interactions alter oxygen delivery in Alzheimer's disease?.- UNCOUPLING PROTEIN-2 IN DIABETIC KIDNEYS: Increased protein expression correlates to increased non-transport related oxygen consumption.- MEASUREMENT OF OXYGENATION AT THE SITE OF STEM CELL THERAPY IN A MURINE MODEL OF MYOCARDIAL INFARCTION.- Oxygen pressures in the interstitial space and their skeletal muscle and tumors in vivo.- B. Other Metabolite Transport in tissue.- ADJUVANT INDUCED GLUCOSE UPTAKE BY ACTIVATED T CELLS IS NOT CORRELATED WITH INCREASED SURVIVAL.- Lactate with oxygen incites angiogeniSIS.- C. Blood, Hemostasis and Hemodynamics.- ACTIVATED PROTEIN C MODULATES CHEMOKINE RESPONSE AND TISSUE INJURY IN EXPERIMENTAL SEPSIS.- MANIPULATION OF THE AFFINITY BETWEEN PROTEIN AND METAL IONS BY IMIDAZOLE AND PH FOR METAL AFFINITY PURIFICATION OF PROTEIN C FROM COHN FRACTION IV-1.- Separation of factor V Leiden molecule, a mutated form of human factor V, from plasma of homozygous patient.- A simple volume related model of arterial blood pressure generation.- D. Tumor, Cancer and Oncology.- STRIKINGLY HIGH RESPIRATORY QUOTIENTS: A FURTHER CHARACTERISTIC OF THE TUMOR PATHOPHYSIOME.- Endogenous hypoxia markers: Case not proven!.- RAD18 SIGNALS DNA POLYMERASE IOTA TO STALLED REPLICATION FORKS IN CELLS ENTERING S-PHASE WITH DNA DAMAGE.- ALANINE IN HI: A SILENT MUTATION CRIES OUT!.- Biomathematics in Cancer Detection: SIMULATION OF LIPOGENESIS IN CANCER.- Activity of drug efflux transporters in tumor cells under hypoxic conditions.- Antioxidants reduce consequences of radiation exposure.- Anti-cancer effect of resveratrol is associated with induction of apoptosisvia a mitochondrial pathway alignment.- E. Tissue Engineering.- Computationally determined shear on cells grown in orbiting culture dishes.- Formation of capillary structure on micro patterned biomaterials.- F. Bio-Instrumentation.- Error analysis of finite-spectral-linewidth illumination in optical oximetry systems.- Changes in the attenuation of near infrared spectra in the healthy adult brain during hypoxaemia cannot be accounted for solely by changes in the concentrations of oxy- and deoxy-haemoglobin.- Assessment of oxygenation and perfusion in the tongue and oral mucosa by visible spectrophotometry and laser doppler flowmetry in healthy subjects.- Cerebral tissue oxygen saturation calculated using spontaneous low frequency hemoglobin oscillations measured by near infrared spectroscopy in adult ventilated patients.- Biosensor for diagnosing factor V leiden, a single amino acid mutated abnormality of factor V.- Scanning laser ophthalmoscope-particle tracking method to assess blood velocity during hypoxia and hyperoxia.- F. Nano-Bio Technology.- Highly sensitive, rapid, reliable, and automatic cardiovascular disease diagnosis with nanoparticle fluorescence enhancer and MEMS.- Tumor specific nano-entity for optical detection and hyperthermia treatment of breast cancer.- LHRH receptor targeted therapy for breast cancer.- G. Translational and Clinical Studies.- Saturation of hemoglobin in intracranial arteries is similar in patients with Hemodynamically relevant and irrelevant stenosis of the internal carotid artery.- A three-tiered approach for calibration of a biosensor to detect estrogen mimics.- Biosensors for Detecting Estrogen-like molecules and protein Biomarkers.- H. Modeling and Analysis of Metabolism and Transport. This section was contributed by the Center for Modeling Integrated Metabolic Systems (MIMS) of the Case Western Reserve University, Cleveland, OH.- MUSCLE OXYGEN UPTAKE DIFFERS FROM CONSUMP

Wound infections occur in approximately 5% of operations. These infections cost the U.K. National Health Service up to £65 million per year and lower patient quality of life. If wound infections could be predicted there would be potential for prevention and a reduction in cost and morbidity would ensue. Work has previously been carried out to predict when these infections will occur, and attempts have been made to create scoring systems for patients undergoing operations. The most simple of these is to classify the type of operation into one of the four following groups

Background Surgical-site infections (SSIs) are common after major abdominal and groin bypass surgery. Tissue oxygen tension has been shown to predict these infections accurately. This study assessed whether a non-invasive measurement of tissue oxygenation, tissue oxygen saturation as measured by spectrophotometry, was as accurate. Methods Fifty-nine patients having major abdominal or groin bypass surgery had tissue oxygen saturation measured by near-infrared spectrophotometry at the incision site and in the arm before operation, and at 12, 24 and 48 h after surgery. Masked outcome assessments for SSI were made at 7 and 30 days after operation. Results In this retrospective analysis, 17 patients (29 per cent) developed an SSI. At 12 h after operation there was a significant difference in tissue oxygen saturation at the surgical site between patients who developed an SSI and those who did not (mean(s.d.) 43·4(18·1) versus 55·8(22·0) per cent; P = 0·032). These oxygen saturation readings were found to be more specific and sensitive in predicting SSIs than the National Nosocomial Infection Surveillance system. Discussion There is a difference in postoperative surgical-site oxygen saturation between patients who subsequently develop SSIs and those who do not. Prediction of SSIs provides opportunities for intervention and prevention.

We have previously demonstrated the successful use of skin oxygen saturation (SO2) measurements to predict the healing viability in lower limb amputations for critical limb ischaemia. The measurements are quick and easy to perform, but the instrument that has been used to date is now obsolete and a new, lightweight, portable instrument has recently been introduced. However, fundamental differences between the two instruments could influence the criteria used for determining amputation level viability. The purpose of this study was to compare the in vivo measurements using the two instruments in order to validate amputation level viability criteria using the RM200.

Monitoring Oxygenation during the Growth of a Transplanted Tumor.- NIRS Measurement of Venous Oxygen Saturation in the Adult Human Head.- What Is Tissue Engineering? What Is ISOTT'S Role?- Lightguide Spectrophotometry to Monitor Free Tram Flaps.- Influence of whole-body vibration static exercise on quadriceps oxygenation.- Indocyanine green Laser retinal oximetry: Preliminary report.- Microcirculation Hemorheology and Tissue Oxygenation in Clinical and Experimental Practice: CEMOT Activity in the Last Two Years.- NIRS-Detected Changes in the Motor Cortex During Mental Rehearsal of Physical Activity (Imaginary Exercise).- NIRS-Detected Changes in the Arm During Mental Rehearsal of Physical Activity (Imaginary Exercise).- Theoretical Simulation of Tumour Oxygenation - Practical Applications.- Application of NIRS in Mice: A Study Comparing the Oxygenation of Cerebral Blood and Main Tissue Oxygenation of Mice and Rat.- Intracellular pH in Gastric and Rectal Tissue Post Cardiac Arrest.- O2 Uptake Kinetics in Skeletal Muscle: Why Is It So Slow and What Does it Mean?- Effects of Major Abdominal Surgery on RBC Deformability.- Post Ischemic No-Reflow After 60 Minutes Hepatic Warm Ischemia In Pigs.- Near Infrared Spectroscopy as a Non-Invasive Assessment of Cortical Abnormality in Migraine?- Biomechanical Design Factor for Soft Gel Chromatography Columns to Separate Homologous, High Molecular Weight, Therapeutic Proteins.- Fluorescence Enhancers for Fluorophore Mediated Biosensors for Cardiovascular Diseaes Diagnosis.- Prediction of Surgical Site Infections Using Spectrophotometry: Preliminary Results.- Relationships Between Muscle SO2, Skin SO2, and Physiological Variables.- Apolipoprotein E Genotype and CBF in Traumatic Brain Injured Patients.- Is Cycloxygenase-2 (cox-2) a Major Component of the Mechanism Responsible for Microvascular Remodeling in the Brain?- Spatially Resolved Blood Oxygenation Measurements Using Time-Resolved Photoacoustic Spectroscopy.- Thermodynamic Approach to Optimize Immobilized Metal Affinity Chromatography Purification of Protein C.- Investigation of Oxygen Saturation Derived from Cardiac Pulsations Measured on the Adult Head Using NIR Spectroscopy.- Focusing on Genomic and Phenomic Aberrations in Non-Melanotic Skin Cancers.- Role of Differences in Microcirculatory Blood Flow Velocity in Optimizing Parameters of the Skeletal Muscle Oxygen Model.- ALU Squences in the Human Respirome.- Assaying ATP Synthase Rotot Activity.- Cancer and the Respirome.- Formation and Role of Nitric Oxide Stores in Adaptation to Hypoxia.- Relationship Between Handgrip Sustained Submaximal Exercise and Prefrontal Cortex Oxygenation.- A Wide Gap Second Derivative NIR Spectroscopic Method for Measuring Tissue Hemoglobin Oxygen Saturation.- Effect of Local Cooling (15oC for 24 hours) with the ChillerpadTM After Traumatic Brain Injury in the Nonhuman Primate.- Safety of Direct Local Cooling (15oC) of the Cerebral Cortex with the ChillerstripTM During Focal Cerebral Ischemia in Monkeys.- Simulation of Mb/Hb in NIRS and Oxygen Gradient in the Human and Canine Skeletal Muscles Using H-NMR and NIRS.- Oxygenation of Cultured Pancreatic Islets.- Diabetes-Induced Decrease in Renal Oxygen Tension: Effects of an Altered Metabolism.- Red Blood Cells (RBC) Deformability and Agregability: Alterations in Alcoholism.- Alteration of Brain Oxygenation During "Piggy Back" Liver Transplantation.- Solutions for Organ Perfusion and Storage: Hemorheological Aspects.- Chronic Hypoxia Modulates Endothelium-Dependent Vasorelaxation through Multiple Independent Mechanisms in Ovine Cranial Arteries.- The "Hemolysis Model" for the Study of Cyto-Toxicity and Cyto-Protection by Bile Salts and Phospholipids.- Exploring Prefrontal Cortex Oxygenation in Schizophrenia by Functional Mear-Infrared Spectroscopy.- Vastus Lateralis Metabolic Response to Explosive Maximal Isometric Leg Press Exercise.- Cost Effective Metal Affinity Chromatography for Protein C Specific, Mini-Antibody Purification.- Brain Injury Following Repetitive Apnea in Newborn Piglets.- Mass Law Predicts Hyperbolic Hypoxic Ventilatory Response.- Quantification of Adult Cerebral Blood Volume Using the NIRS Tissue Oxygenation Index.- Preliminary Study of Fiber Optic Multi-Cardiac-Marker Biosensing System for Rapid Coronary Heart Disease Diagnosis and Prognosis.- Changes in Perfusion Pattern of Experimental Tumors Due to Reduction in Arterial Oxygen Partial Pressure.- Theoretical Simulation of Tumour Hypoxia Measurements.- Preliminary Results of Oxygen Saturation with a Prototype of Continuous Wave Laser Oximeter.- Cerebral Oxygenation and Push-Pull Effect.- Impact of Hemarheological and Endothelial Factors on Microcirculation.- Artepillin C Isoprenomics: Design and Synthesis of Artepillin C Analogues as Antiatherogenic Antioxidants.- Imaging Oxygen Pressure in the Rodent Retina by Phosphorescence Lifetime.- Do Slow and Small Oxygen Changes Affect the Cerebral Cytochrome Oxidase Redox State Measured by Near-Infrared Spectroscopy?- Relationship Between Carbon Dioxide Eliminaiton Kinetics and Metabolic Correlates of Oxygen Debt in Septic Patients.- Index.

This paper presents the technology and some experiments results of a novel Rapid Prototyping/Tooling/Manufacture (RP/RT/RM) process, Shell Assisted Layer Manufacturing (SALM), which is based on layer manufacturing technology (LMT). The SALM process executes two essential steps to develop one layer of the part. Initially, it develops the outer shell (boundaries) of the particular layer of the part using the Fused Deposition Modelling (FDM) technique and then the shell is filled with UV (Ultraviolet) curable resin. The deposited resin layer is then cured using a UV light source. This procedure is repeated until the complete part is built. The process has the potential to give improved quality, productivity and process speed.

It is has been estimated that hospital acquired (nosocomial) infections cost the National Health Service (NHS), in England alone, £931 million per annum.1 Of this, the cost of lower limb wound infections (which account for about 21% of all surgical wound infections) can be calculated at £13.7 million per annum. Thus, the development of techniques that can quantify the risk of infection and thus allow early preventative treatment is desirable on both clinical and economic grounds.

Medical infrared thermographic imaging has been applied in the past to areas such as detection of breast tumours, deep vein thrombosis and lower limb amputation level assessment. In almost all instances problems were encountered which meant that the technique could not be used alone diagnostically without the support of other tests, and has consequently only found a limited number of applications. In the present study, thermographic images were recorded dynamically during the reheating of skin following cooling to 25°C. Pixel-by-pixel component analysis ofthe images was carried out offline in order to construct the functional parametric images. Normal volunteers were investigated using dynamic thermographic imaging ofthe left volar forearm skin under different experimental conditions. In a further pilot study 6 patients with known tumours were studied in order to investigate whether the lesions could be characterised by abnormalities in the parametric images. The resultant parametric images display information on the heterogeneity of skin blood flow in the areas examined. The heterogeneities observed are very much greater than those obtained with static thermographic images and characteristic patterns appear to emerge under the different experimental conditions. in particular, the early parametric images of breast tumours indicate clear characteristic patterns.

About 5% of British males over 50 years develop peripheral arterial occlusive disease. Of these about 2% ultimately require lower limb amputation. In 1995 we proposed a new technique using lightguide spectrophotometry to measure the oxygen saturation level of haemoglobin (SO2) in the skin as a method for predicting tissue viability. This technique, in combination with thermographic imaging, was compared with skin blood flow measurements using the I125)4- Iodoantipyrine (IAP) clearance technique. The optical techniques gave a sensitivity and selectivity of 1.0 for the prediction of successful outcome of a below knee amputation compared with a specificity of 93% using the traditional IAP technique at a below knee to above knee amputation ratio (BKA:AKA) of 75%. The present study assesses the routine clinical application of these optical techniques. The study is ongoing, but the data to date comprises 22 patients. 4 patients were recommended for above knee amputation (AKA) and 18 patients for below knee amputation on the basis of thermographic and tissue SO2 measurements. All but one of the predicted BKA amputations healed. The study to date produces evidence of 94% healing rate (specificity) for a BKA:AKA ratio of 82%. This compares favorably with the previous figures given above.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

p21WAF1/CIP1 is a nucleoprotein that was initially characterized by its ability to be regulated transcriptionally by p53 and by its ability to mediate growth arrest by binding to cyclin-dependent kinases. Although p21WAF1/CIP1 is thought to mediate the effects of p53 in causing growth arrest, p21WAF1/CIP1 is also regulated in a p53-independent manner, e.g., during terminal differentiation of some cell lines. Growth factors including epidermal growth factor also induce p21WAF1/CIP1 through p53-independent pathways. Because the epidermal growth factor signaling pathway is abnormal in psoriatic epidermis, we studied p21WAF1/CIP1 expression, using in situ hybridization and immunohistochemistry, in psoriasis. Both p21WAF1/CIP1 mRNA and protein were significantly elevated in untreated psoriatic plaques compared with uninvolved psoriatic skin (p < 0.0001), with the up-regulation of p21WAF1/CIP1 being predominantly suprabasal. This increase was accompanied by a small increase in p53 protein expression of uncertain significance. Furthermore, p21WAF1/CIP1 expression was induced in skin after sellotape stripping and by the application of agents, such as dithranol, that are capable of inducing hyperproliferation. The pattern of p21WAF1/CIP1 expression observed is consistent with a role in induction and maintenance of differentiation. Our experiments, however, cannot determine whether the abnormalities of p21WAF1/CIP1 epidermal expression in psoriasis and after insult are independent of changes in p53 expression.