2D core ion temperature and impurity density measurements with Coherence Imaging Charge Exchange Recombination Spectroscopy (CICERS) at Wendelstein 7-X (invited).

Coherence Imaging Charge Exchange Recombination Spectroscopy (CICERS) is an imaging diagnostic installed in Wendelstein 7-X from which 2D maps of ion temperature (Ti) and impurity density (nZ) are obtained. The improved spatial resolution and coverage, as compared to standard Charge eXchange Recombination Spectroscopy (CXRS), with which these parameters can be assessed, come at the expense of spectral resolution, requiring the development of new strategies to isolate the active charge exchange contribution from passive and Bremsstrahlung radiation. In this work, a new approach based on the modeling of background radiation is presented and applied to the derivation of 2D Ti maps. These are compared to the Ti profiles derived from standard CXRS, which found excellent agreement up to the edge (ρ > 0.8). The CICERS view is implemented in the pyFIDAsim code, which is used to provide further insight into the spatial localization of the radiation as measured by the diagnostic. Moreover, an absolute intensity calibration is carried out, and, coupled with pyFIDAsim, the first 2D nC maps are obtained and validated against CXRS data.

Initial beam emission spectroscopy diagnostic system on HL-2A tokamak.

A beam emission spectroscopy system is being developed and deployed on the HL-2A tokamak to measure local low wavenumber (k ⊥ ρ i < 1) density fluctuations by measuring the Doppler-shifted emission from a 50 kV deuterium heating neutral beam. High spatial resolution (Δr ≤ 1 cm, Δz ≤ 1.5 cm) measurements are achieved with customized in-vacuum optics. High frequency, high-gain preamplifiers sample the light intensity at a Nyquist frequency of 1 MHz and achieve a high S/N ratio via high optical throughput, low-noise preamplifiers, and high quantum efficiency photodiodes. A first set of 16 detector channels [configured in an 8 (radial) × 2 (poloidal) array] has been installed and tested at HL-2A, covering the radial range r/a = 0.8-1.1. The frequency and wavenumber spectra have been measured under different plasma conditions. Initial measurements have demonstrated the capability of measuring edge plasma density fluctuation spectra and the poloidal flow velocity fields with a high S/N ratio.

Drug treatment of canine acral lick. An animal model of obsessive-compulsive disorder.

Canine acral lick dermatitis is a naturally occurring disorder in which excessive licking of paws or flank can produce ulcers and infection that require medical treatment. Forty-two dogs with severe chronic canine acral lick dermatitis were treated in three double-blind crossover comparisons of clomipramine hydrochloride/desipramine hydrochloride, fluoxetine hydrochloride/fenfluramine hydrochloride, and sertraline hydrochloride/placebo. The serotonin uptake blocking drugs were clinically effective, while the other drugs were not. Based on phenomenology and pharmacological response, we propose canine acral lick dermatitis as an animal model of obsessive-compulsive disorder.

Construction and in vivo efficacy of a replication-deficient recombinant adenovirus encoding murine growth hormone.

We have constructed a recombinant, replication-deficient, first-generation adenovirus-encoding mouse GH (mGH), AdCMVmGH. This virus directed mGH production from an epithelial cell line in vitro in a dose-dependent manner. When injected into the quadriceps muscle or submandibular ducts of mGH-deficient Snell dwarf mice, AdCMVmGH resulted in the production of significantly elevated serum mGH levels. Furthermore, after i.m. injection, dwarf mice increased in weight by 8% over 4 days and close to 100% by 30 days. When AdCMVmGH was administered to 3- to 4-week-old rats by i.v. injection to assess general metabolic responses, serum mGH, insulin-like growth factor 1, triglycerides and cholesterol levels were significantly elevated. AdCMVmGH should be a valuable experimental tool for the controlled, directed expression of mGH in preclinical mouse model studies.

Tissue compatibility of two biodegradable tubular scaffolds implanted adjacent to skin or buccal mucosa in mice.

Radiation therapy for cancer in the head and neck region leads to a marked loss of salivary gland parenchyma, resulting in a severe reduction of salivary secretions. Currently, there is no satisfactory treatment for these patients. To address this problem, we are using both tissue engineering and gene transfer principles to develop an orally implantable, artificial fluid-secreting device. In the present study, we examined the tissue compatibility of two biodegradable substrata potentially useful in fabricating such a device. We implanted in Balb/c mice tubular scaffolds of poly-L-lactic acid (PLLA), poly-glycolic acid coated with PLLA (PGA/PLLA), or nothing (sham-operated controls) either beneath the skin on the back, a site widely used in earlier toxicity and biocompatibility studies, or adjacent to the buccal mucosa, a site quite different functionally and immunologically. At 1, 3, 7, 14, and 28 days postimplantation, implant sites were examined histologically, and systemic responses were assessed by conventional clinical chemistry and hematology analyses. Inflammatory responses in the connective tissue were similar regardless of site or type of polymer implant used. However, inflammatory reactions were shorter and without epithelioid and giant cells in sham-operated controls. Also, biodegradation proceeded more slowly with the PLLA tubules than with the PGA/PLLA tubules. No significant changes in clinical chemistry and hematology were seen due to the implantation of tubular scaffolds. These results indicate that the tissue responses to PLLA and PGA/PLLA scaffolds are generally similar in areas subjacent to skin in the back and oral cavity. However, these studies also identified several potentially significant concerns that must be addressed prior to initiating any clinical applications of this device.

Treatment of uveitis with recombinant human interleukin-13.

AIM: To evaluate the anti-inflammatory cytokine interleukin-13 (IL-13) for the treatment of uveitis. METHODS: Uveitis was induced in monkeys by immunisation with human retinal S-antigen. Starting at the onset of disease, the animals were treated with IL-13 at 25 micrograms/kg, or vehicle control, injected subcutaneously once a day for 28 days. Intraocular inflammation was scored by indirect ophthalmoscopy for a period of 56 days. Circulating leucocyte levels were monitored. RESULTS: Uveitis started unilaterally in all but one animal. IL-13 inhibited inflammation both in the eyes in which the disease was present when the treatment was initiated (p = 0.0001), and in the contralateral initially negative eyes (p = 0.0001). After cessation of therapy, there was a progressive increase of inflammation in the IL-13 treated group. However, the beneficial effect of IL-13 extended into the 4 week follow up period. IL-13 produced an increase in circulating polymorphonuclear neutrophils and a decrease in lymphocytes. CONCLUSION: Administration of IL-13 appears to be a promising modality of treatment for severe uveitis.

NOD mouse model for Sjögren's syndrome: lack of longitudinal stability.

OBJECTIVES: The non-obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjögren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno-associated viral (rAAV2) vector transfer of immunomodulatory transgenes to alter the SS-like disease in NOD mice. Data collected over a 2-year period indicated a changing SS phenotype in these mice and this phenomenon was investigated. METHODS: 10(10) particles rAAV2LacZ/gland were delivered to both submandibular glands (SMGs) of NOD/LtJ mice at 8 weeks (before sialadenitis onset) of age. Salivary flow rates were determined at 8 weeks and time of killing. Blood glucose levels and body weights were measured weekly. After killing, saliva and SMGs were harvested. Analyses of salivary output, inflammatory infiltrates (focus score), SMG cytokine profile, body weight, and diabetes mellitus status were performed. Data from six different experimental studies over 2 years were analyzed and compared. RESULTS: Salivary flow rate, focus score, and SMG cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12(p70), tumor necrosis factor-alpha and IFNgamma showed changes over time. There were no differences for body weight, diabetes mellitus prevalence, or blood glucose level of non-diabetic mice. CONCLUSION: This retrospective report is the first to describe longitudinal variability in the NOD mouse as a model for SS. We advise other investigators to continuously monitor the SS phenotype parameters and include appropriate controls when studying this disease in NOD mice.

Development of iron deficiency anemia in infant rhesus macaques.

Although previous research has documented the occurrence of an iron deficiency anemia in infant nonhuman primates, the temporal development of this condition has not been studied to our knowledge. We conducted a retrospective analysis of complete blood count data obtained from 56 rhesus macaque infants over a 5-month period. Fourteen infants were exclusively mother-reared, and 42 were nursery-reared. By 60 days of age, erythrocyte indices were lower in the mother-reared monkeys than in the nursery-reared animals. Between 90 to 150 days of age, an apparent iron deficiency anemia developed in the mother-reared infants only. This anemia was characterized as a microcytic, hypochromic anemia. The time of onset of this anemia was comparable developmentally to that observed in exclusively breast-fed human infants. At no time were these infants clinically or behaviorally affected by the anemia. Hematologic status of the mothers did not correlate with that of their infants. It could not be determined whether mother's parity was predictive of the development of anemia in the infant. These observed phenomena in rhesus monkeys may serve as a potential nonhuman primate model for the anemia that is observed in exclusively breast-fed human infants.

Humanized antibodies against the alpha-chain of the IL-2 receptor and against the beta-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases.

We studied the efficacy and tolerance of humanized Ab interfering with the signal of the IL-2 and IL-15 receptors in a primate model of experimental autoimmune uveoretinitis. The inhibitory effects of humanized anti-Tac (HAT), an anti-IL-2R alpha-chain Ab, and HuMik beta1, an Ab directed at the beta-chain shared by the receptors of IL-2 and IL-15, were tested in culture on the proliferative response of monkey Con A-blast lymphocytes stimulated with IL-2 or IL-15. Uveitis was induced in cynomolgus monkeys by immunization with human recombinant retinal S-antigen. Treatment was initiated at the first sign of disease and consisted of HAT and HuMik beta1, alone or in combination, or vehicle control given by i.v. injection twice a week for 4 wk. Disease was evaluated by ocular funduscopy. The results in culture showed a significant dose-dependent inhibition of the IL-2-driven proliferation of lymphocytes by HAT. HuMik beta1 alone was ineffective against IL-2 stimulation, but had a marked potentiating effect in combination with HAT, independent of IL-15 signaling. IL-15-driven proliferation was inhibited by HuMik beta1, but not by HAT alone or in combination. In monkeys, experimental autoimmune uveoretinitis evolution was significantly inhibited by HAT treatment. HuMik beta1 alone had no effect on the disease. However, when used in combination, the two Ab markedly reduced the severity of ocular inflammation. The Ab were well tolerated. Only three monkeys, treated with HAT alone, made an Ab response against the injected Ab.