Quality of CD8+ T cell immunity evoked in lymph nodes is compartmentalized by route of antigen transport and functional in tumor context.

Revealing the mechanisms that underlie the expansion of antitumor CD8+ T cells that are associated with improved clinical outcomes is critical to improving immunotherapeutic management of melanoma. How the lymphatic system, which orchestrates the complex sensing of antigen by lymphocytes to mount an adaptive immune response, facilitates this response in the context of malignancy is incompletely understood. To delineate the effects of lymphatic transport and tumor-induced lymphatic and lymph node (LN) remodeling on the elicitation of CD8+ T cell immunity within LNs, we designed a suite of nanoscale biomaterial tools enabling the quantification of antigen access and presentation within the LN and resulting influence on T cell functions. The expansion of antigen-specific stem-like and cytotoxic CD8+ T cell pools was revealed to be sensitive to the mechanism of lymphatic transport to LNs, demonstrating the potential for nanoengineering strategies targeting LNs to optimize cancer immunotherapy in eliciting antitumor CD8+ T cell immunity.

Localized SDF-1α Delivery Increases Pro-Healing Bone Marrow-Derived Cells in the Supraspinatus Muscle Following Severe Rotator Cuff Injury.

To examine how the chemotactic agent stromal cell-derived factor-1alpha (SDF-1α) modulates the unique cellular milieu within rotator cuff muscle following tendon injury, we developed an injectable, heparin-based microparticle platform to locally present SDF-1α within the supraspinatus muscle following severe rotator cuff injury. SDF-1α loaded, degradable, N-desulfated heparin-based microparticles were fabricated, injected into a rat model of severe rotator cuff injury, and were retained for up to 7 days at the site. The resultant inflammatory cell and mesenchymal stem cell populations were analyzed compared to uninjured contralateral controls and, after 7 days, the fold-change in anti-inflammatory, M2-like macrophages (CD11b+CD68+CD163+, 4.3X fold-change) and mesenchymal stem cells (CD29+CD44+CD90+, 3.0X, respectively) was significantly greater in muscles treated with SDF-1α loaded microparticles than unloaded microparticles or injury alone. Our results indicate that SDF-1α loaded microparticles may be a novel approach to shift the cellular composition within the supraspinatus muscle and create a more pro-regenerative milieu, which may provide a platform to improve muscle repair following rotator cuff injury in the future.

Sangye Gyatso (1653-1705) and the medical paintings of Tibet.

Sangye Gyatso played a major role in the politics of 17th century Tibet, and was the originator of the medical paintings that encompassed the full scope of Tibetan medicine.The depictions became an important aid in medical education, and was heavily influenced by Buddhist thinking. The paintings arose in a visual culture dominated by religious art.

The death of Buddha: a medical enquiry.

The death of the Buddha (Siddhartha Gautama) has been depicted widely in Buddhist iconography. The Buddha is generally shown with a serene or smiling expression, lying on his right side and resting his head on his right hand. The dates of Buddha's life traditionally are given as 566-486 BC. Buddha died from an illness, the nature of which remains unsettled. The present paper examines a variety of sources and concludes that it was tainted pork that led to his demise. He succumbed to the disease pig-bel, a necrotizing enteritis caused by the toxins of Clostridium perfringens infection.

The healing Buddha.

The iconography of the healing Buddha embraces two healing traditions, symbolized by the healing stone lapis lazuli from Central Asia and by the myrobalan fruit from the ayurvedic medicine of ancient India. The first mention of the healing Buddha is in Buddhist texts of the first century BC, and the earliest extant icons date from the fourth century AD. This suggests the cult of the healing Buddha was a relatively late development in the history of Buddhism. Worshippers sought his help in alleviating spiritual, mental and physical suffering, as well as for medical cures. In China followers believed he was also a cosmic Buddha, to whom one appealed for longevity and protection from disasters. This form of faith-based healing remains vibrant in China, Japan and Tibet to this day.

Physical performance evaluation of the Toshiba GCA-9300A triple-headed system.

The physical performance of the Toshiba GCA-9300A triple-headed SPECT system has been assessed. Using a water-filled cylinder containing 99mTc, the tomographic volume sensitivity was 33.8 and 34.8 kcps/(MBq/ml)/cm for the high-resolution, parallel-hole (HR-PH) collimator and the super high-resolution, lead fanbeam (SHR-FB) collimator, respectively, excluding the rotation time(s) during scanning when data are not acquired. The tomographic spatial resolution at the center, in air, with 132 mm radius of rotation was 10.2 and 7.8 mm FWHM with the HR-PH and SHR-FB collimators, respectively; in water it was 11.0 and 7.8 mm. Reconstructed relative activity concentrations were accurate for both collimator sets if attenuation correction was used. With the SHR-FB collimators, the average peak-to-valley ratio of five-line sources in water improved significantly when an asymmetric energy window was used. Using the three-dimensional Hoffman brain phantom which simulates a 4:1 grey matter-to-white matter ratio and the usual choice of acquisition and processing parameters for brain studies, the reconstructed grey matter-to-white matter ratio was only about 1.7 for total counts typically acquired in a 99mTc-HMPAO study (4.0 M counts) and only 2.3 for 40 M counts. There was a qualitative improvement with an asymmetric energy window.

Cardiovascular and ventilatory responses to dynamic exercise during epidural anaesthesia in man.

1. In order to evaluate the importance of afferent neural feedback from the working muscles for cardiovascular and ventilatory responses to dynamic exercise, epidural anaesthesia was induced at L3-L4. Six healthy males cycled for 20 min at 57% of maximum oxygen uptake and for 8-12 min at increasing work intensities until exhaustion at 238 +/- 30 W without as well as with epidural anaesthesia. 2. Presence of afferent neural blockade was verified by cutaneous sensory analgesia below T10-T11 and attenuated post-exercise ischaemic pressor response (45 +/- 8-24 +/- 6 mmHg). Efferent sympathetic nerves appear to be intact since basal heart rate and blood pressure as well as the cardiovascular responses to a Valsalva manoeuvre and to a cold pressor test were unchanged. 3. During dynamic exercise with epidural anaesthesia, blood pressure was lower than in control experiments; however, ventilation and heart rate were not affected. 4. The results indicate that afferent neural activity from the working muscles is important for blood pressure regulation during dynamic exercise in man but may not be necessary for eliciting the ventilatory and heart rate responses.

Cerebral blood flow during submaximal and maximal dynamic exercise in humans.

Cerebral blood flow (CBF) in humans was measured at rest and during dynamic exercise on a cycle ergometer corresponding to 56% (range 27-85) of maximal O2 uptake (VO2max). Exercise bouts were performed by 16 male and female subjects, lasted 15 min each, and were carried out in a semisupine position. CBF (133Xe clearance) was expressed as the initial slope index (ISI) and as the first compartment flow (F1). CBF at rest [ISI, 58 (range 45-73); F1, 76 (range 55-98) ml.100 g-1.min-1] increased during exercise [ISI to 79 (57-94) and F1 to 118 (75-164) ml.100 g-1.min-1, P less than 0.01]. CBF did not differ significantly between work loads from 32 (24-33) to 86% (74-96) of VO2max (n = 10). During exercise, mean arterial pressure increased from 84 (60-100) to 101 (78-124) Torr (P less than 0.01) and PCO2 remained unchanged [5.1 (4.6-5.6) vs. 5.4 (4.4-6.3) kPa, n = 6]. These results demonstrate a median increase of 31% (0-87) in CBF by ISI and a median increase of 58% (0-133) in CBF by F1 during dynamic exercise in humans.