Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.     

Fat extraction from acid- and base-hydrolyzed food samples using accelerated solvent extraction

This paper describes a new in-cell method for pursuing accelerated solvent extraction (ASE) prior to lipid analysis from food samples. It is difficult to pursue direct ASE with acid- or base-hydrolyzed samples due to the corrosive nature of the reagents and material limitations. In this study ion exchange based materials were used to remove acid or base reagents in-cell without compromising the recovery of lipids. The performance data are presented here for the new methods for lipid extraction for a variety of food samples and compared to the Mojonnier method. NIST Standard Reference Materials (SRM-1546 and SRM-1849) were used to validate the ASE methods. Excellent fat recoveries were obtained for the ASE methods. The new methods presented here enhance the utility of ASE and eliminate labor intensive protocols.     

Systematic landscape restoration using integer programming

In some agricultural regions, reservation of remnant natural lands will not maintain the natural biodiversity and large-scale ecological restoration is required. Geographic planning for restoration is essential to obtain the maximum ecological benefit from the limited resources available for landscape restoration. In this paper, we present a proof-of-concept that implements principles of systematic conservation planning, such as adequacy, representativeness, efficiency and flexibility, within an integer programming framework to identify geographic priorities for landscape restoration in a small catchment in South Australia. Integer programming ensures maximally efficient solutions that meet conservation targets in the form of minimum proportions (30%) and minimum areas (15 ha) of each environment type. However, the optimum solution identifies a system of scattered sites with an inadequate and impractical landscape structure. We propose a system of impedance surfaces that prioritise the spatial location of restoration towards improving landscape structure. Different options for systematic landscape restoration are assessed and the costs of spatial prioritisation of areas is found to be either optimal or very near optimal regardless of the impedances used. Thus, the cost of spatial prioritisation of sites for restoration in the landscape is negligible. We suggest the proposed methodology fits within a broader plan for landscape restoration and natural resource management.     

A serological comparison of complement fixation reactions using Brucella abortus and B. melitensis antigens in B. abortus infected cattle

Brucella abortus and B. melitensis antigens were used in parallel on the National Standard Brucella abortus antiserum and on field sera coming from cattle where practically exclusively B. abortus biotypes 1 and 2 have been isolated over the last 11 years. With the National Standard serum the titres to B. melitensis were consistently lower than those to B. abortus antigen. Most were 1 dilution (twofold) lower. Although a similar trend was seen with the field sera, there were 7/346 sera which had twofold or higher titres to B. melitensis antigen. Although this may be due to the vagaries of the test it also warrants closer investigation of the animals concerned to see whether M-antigen predominant Brucella biotypes are possibly present. The use of the dual antigens could identify herds which are infected only with A-antigen predominant brucellae but would not be reliable for classifying individual animals.     

ULTRASONIC DETERMINATION OF KIDNEY VOLUME IN THE DOG

Canine kidney measurements were obtained in vivo using ultrasound before and after anesthesia and were compared with direct caliper measurements at laparotomy. Following excision, the kidney dimensions were also measured ultrasonically in a water bath and the results were used to calculate kidney -volume by a modified parallel planimetric method and three variations of a prolate ellipsoid method. The calculated volume was compared with actual kidney volume determined by volume displacement. All methods were found to underestimate actual volume so that a linear correction of ultrasonically calculated volume was required to predict actual volume. The modified parallel planimetric method and a prolate ellipsoid method using height and width determinations cranial and caudal to the renal pelvis were the best models. The prolate ellipsoid model was chosen for subsequent kidney volume calculations because of its simplicity. The noninvasive calculation of kidney volume using ultrasound was sufficiently accurate to be clinically useful, particularly when serially evaluating kidney size changes in the same dog.     

ESTIMATION OF PORTAL BLOOD FLOW USING DUPLEX REAL-TIME AND PULSED DOPPLER ULTRASOUND IMAGING IN THE DOG

A duplex ultrasound system incorporating a pulsed wave Doppler ultrasound probe with conventional B-mode real-time imaging was used to evaluate portal vein blood flow in eight normal dogs. Adequate visualization of the cranial abdominal vessels was obtained from the right lateral 11th or 12th intercostal space. Doppler spectral analysis showed non-pulsatile flow with a wide range of linear flow velocities across the vessel lumen typical of laminar blood flow. Results for portal vein blood flows were 49.8 ± 13.5 ml/min/kg body weight (mean ± SD) with a range of 37.8 - 76.8 ml/min/kg body weight. These values overestimate portal blood flow by approximately 2 times when compared with published studies using invasive techniques. This overestimation is primarily due to the use of the maximal flow velocity in the blood flow calculations.     

Evaluation of a regimen using a progesterone releasing intravaginal device (CIDR) and PMSG as a treatment for post partum anoestrus in dairy cattle

Anoestrous dairy cows in seasonally calving herds in the Macalister Irrigation District of Gippsland, Victoria were treated at the start of the mating period with a progesterone releasing intravaginal device (CIDR). The CIDR was inserted for 7 days and 400 IU of PMSG was injected intramuscularly at removal. There was no clinically useful difference among cows receiving the CIDR, a placebo and untreated cows in the interval from treatment to either first oestrus or conception, the conception rate to first service or percent pregnant by the end of mating. Analyses of data from 2-year-old cows, older cattle, cows calved at least 45 days or cows calved at least 55 days and cows treated 3 weeks after the start of mating did not show improved reproductive performance following treatment with the CIDR.     

Cohenite in meteorites: a proposed origin

Cohenite [(Fe, Ni)(3)C] is found almost exclusively in meteorites containing from 6 to 8 percent nickel (by weight). On the basis of iron-nickel-carbon phase diagrams at 1 atmosphere and of kinetic data, the occurrence of cohenite within this narrow composition range as a low-pressure metastable phase and the nonoccurrence of cohenite in meteorites outside the range 6 to 8 percent nickel can be explained. Cohenite formed in meteorites containing less than 6 to 8 percent nickel decomposed to metal and graphite during cooling; it cannot form in meteorites containing more than about 8 percent. The presence of cohenite in meteorites cannot be used as an indicator of pressure of formation. However, the absence of cohenite in meteorites containing the assemblage, metal plus graphite, requires low pressures during cooling.     

Idiopathic pericarditis and cardiac tamponade in two cows

Idiopathic pericarditis is an uncommon diagnosis in cattle with cardiac tamponade. Two cows were examined for clinical signs of right-sided congestive heart failure, including tachycardia, venous distention, and peripheral edema. Muffled heart sounds were detected in one of the cows. Echocardiography in both cows revealed voluminous anechoic pericardial effusion and compression of the right atrium and right ventricle. Cytologic analysis of the pericardial fluid revealed hemorrhagic inflammation but no evidence of a septic or neoplastic condition such as traumatic reticulopericarditis or lymphoma, respectively. Pericardial drainage and lavage accompanied by treatment with anti-inflammatory drugs were curative in both cows. It is important to differentiate cows with idiopathic pericarditis from cows with more common septic pericarditis because the prognosis for the former disease appears to be good with appropriate treatment.