A peptide sequence from platelet factor 4 (CT-112) is effective in the treatment of type II collagen induced arthritis in mice

OBJECTIVE: Platelet factor 4 (PF-4) is a critical alpha chemokine in inflammation and injury responses, with multiple effects upon cellular activities. Discrete peptide sequences of the PF-4 molecule have been shown to retain biological activity. Our aim was to examine the influence of the PF-4 derived octapeptide (CT-112; TTSQVRPR) on type II collagen induced arthritis in mice, to determine if this peptide exhibited antiinflammatory properties. METHODS: DBA/1 mice were treated with CT-112 from either the time of immunization with type II collagen or from the initial onset of arthritis. RESULTS: CT-112 both prevented the development of arthritis in mice treated prophylactically and reduced progression of disease in animals treated therapeutically, and was active when delivered by either subcutaneous injection or oral gavage. No marked immunosuppressive effects were observed during CT-112 treatment, with only moderate decrease in antibody levels and mitogen responses. A significant reduction of the circulating levels of IL-1 was a consistent finding in mice treated therapeutically with CT-112. CONCLUSION: These data suggest PF-4 derived octapeptide exerts antiinflammatory effects of experimental arthritis in mice.     

Preparation of cryoprecipitated factor VIII concentrates

Factors affecting the yield of factor VIII in cryoprecipitate have been investigated in the context of a blood component program. Both in vitro and in vivo measurements were used to assess the effects of critical variables on the yield of factor VIII activity. Variables such as anticoagulant, plastic bag, mixing during collection, and platelet contamination had no significant effect on yield of factor VIII activity in cryoprecipitate. Among the most critical factors affecting yield were storage time of whole blood and procedures for freezing, thawing, and reconstitution. The following procedures were found to assure a 60 per cent recovery of factor VIII in cryoprecipitate: 1)processing of whole blood within six hours of collection; 2)use of a technique to freeze plasma within 30 minutes either in a -70 C ethanol bath or -85 C freezer; 3)rapid thawing (1 1/2 hour or less) in a 4 C circulating water bath; 4)centrifugation at 4,500 X g for 10 minutes at 4 C followed by draining of the supernatant in a 4 C cold room; 5) storage of the precipitate at -20 C until ready for use; 6) thawing in a 37 C water bath for at least 15 minutes followed by addition of 20 ml of 0.15 M saline for a 20 minute period at room temperature, and gentle mixing before pooling units for transfusion. The recovery of factor VIII in cryoprecipitate appears to be limited to about 65 per cent by its solubility in plasma at 4 C. Therefore, further effort to increase the amount available for treatment should involve improving the supply of plasma for its preparation and decreasing the cost of processing.     

Axial wave propagation in membrane shells of revolution

The dynamic finite element technique, which is referred to in the literature as ‘computer-analysis’, is applied to wave propagation problems occurring in finite and semi-infinite linearly elastic membranes of revolution. Both semi-infinite and finite versions of cylindrical and conical membranes are considered, and a finite membrane having a meridional curve which is parabolic is solved. The source of excitation is generally a constant velocity motion of one end of the membranes, but the results for a stress-pulse input at one end of a semi-infinite cylindrical membrane are also given. The results for the finite membranes are new, and the results for the semi-infinite problems are discussed with respect to previously published results. The two-dimensional state of stress in the membrane requires careful ordering of the calculations, and the boundary conditions for finite membranes are shown to follow logically from this ordering of the calculations. The difference in the solutions resulting from prescribing an axial or a tangential velocity excitation at the end of a conical membrane is presented, and the mesh size necessary for convergence to the solution is indicated. The graphs of the results clearly indicate regions in space and time where the membrane model should be replaced by the shell formulation to represent a realistic structure. The technique is shown to be self-contained and independent of any formal method such as the method of characteristics.     

Using ab initio calculations in designing bcc Mg–Li alloys for ultra-lightweight applications

Ab initio calculations are becoming increasingly useful to engineers interested in designing new alloys, because these calculations are able to accurately predict basic material properties only knowing the atomic composition of the material. In this paper, single crystal elastic constants of 11 bcc Mg–Li alloys are calculated using density functional theory (DFT) and compared with available experimental data. Based on DFT determined properties, engineering parameters such as the ratio of bulk modulus over shear modulus (B/G) and the ratio of Young’s modulus over mass density (Y/ρ) are calculated. Analysis of B/G and Y/ρ shows that bcc Mg–Li alloys with 30–50 at.% Li offer the most potential as lightweight structural material. Compared with fcc Al–Li alloys, bcc Mg–Li alloys have a lower B/G ratio, but a comparable Y/ρ ratio. An Ashby map containing Y/ρ vs B/G shows that it is not possible to increase both Y/ρ and B/G by changing only the composition of a binary alloy.     

Comparison of photocurrent enhancement and upset enhancement inCMOS devices in a medium-energy X-ray environment

Radiation-induced upset levels in SA3001 static random access memories (SRAMs) and SA3246 clock integrated circuits (ICs) have been measured in a medium-energy flash X-ray environment (average photon energy ~100 keV), where dose-enhancing effects are very important. By comparing device responses using a non-dose-enhancing ceramic package lid and a dose-enhancing Kovar/gold lid, dose-enhancement factors for photocurrent and upset were generated. The observed upset enhancement factors of 3.0±0.5 (SRAM) and 2.2±0.2 (clock IC) are in excellent agreement with measurements of photocurrent enhancement factors (2.5±0.5) in diodes processed with the same diffusions as the complementary metal-oxide-semiconductor (CMOS) ICs irradiated in a steady-state X-ray environment. These results indicate that upset is dominated by the radiation-induced transient supply current in these ICs, and that steady-state diode photocurrent measurements are a good predictor of both photocurrent and upset enhancement for ICs made with this technology     

Urinary cyclic adenosine 3',5'-monophosphate response in McCune-Albright syndrome: clinical evidence for altered renal adenylate cyclase activity

The recent finding of an activating mutation in the Gs alpha protein, the protein that couples receptors to stimulation of adenylate cyclase, from endocrine and nonendocrine tissues of patients with McCune-Albright syndrome (MAS) suggests that alterations in adenylate cyclase activity may account for the clinical abnormalities in these patients. Many patients with MAS have hypophosphatemia. This may result from the presence of the activating Gs alpha mutation in proximal renal tubules or the elaboration of a phosphaturic factor from fibrous dysplasia. We, therefore, sought to characterize renal cAMP generation and phosphate handling in MAS patients. Intravenous infusion of PTH is a classic clinical test used to evaluate hormonal responsiveness of renal proximal tubule adenylate cyclase and examine PTH-dependent phosphate clearance. We performed PTH infusion in 6 MAS patients, 10 normal subjects, and 6 patients with pseudohypoparathyroidism (PHP). The basal urinary cAMP (UcAMP) level in the MAS group [5.5 +/- 2.6 nmol/dL glomerular filtration (GF)] was elevated (P < 0.05) compared to those in both normal subjects (3.2 +/- 1.2 nmol/dL GF) and patients with PHP (1.9 +/- 0.6 nmol/dL GF). However, PTH-stimulated peak UcAMP (15.0 +/- 7.0 nmol/dL GF) and the peak/basal UcAMP ratio (3.1 +/- 1.7) in MAS were significantly lower than the respective values in normal subjects (30.8 +/- 16.9 nmol/dL GF and 9.3 +/- 2.9; P < 0.05 for both) and were statistically similar to the blunted levels in PHP (respectively, 3.1 +/- 1.5 nmol/dL GF and 2.0 +/- 1.7). By contrast, the PTH-induced phosphaturic response in MAS patients was similar to that in the normal subjects. Our study provides clinical evidence that MAS patients have altered renal adenylate cyclase activity, manifested by an elevated basal UcAMP, but a blunted UcAMP response to PTH stimulation. These observations are presumably due to a mutation in the Gs alpha protein in the renal tubules. Despite the blunted UcAMP excretion, the phosphaturic response to PTH in MAS patients is intact.     

Using Ab Initio Calculations in Designing bcc MgLi–X Alloys for Ultra‐Lightweight Applications

Body centered cubic (bcc) Mg–Li‐based alloys are a promising light‐weight structural material. In order to tailor the Mg–Li composition with respect to specific industrial requirements, systematic materials‐design concepts need to be developed and applied. Quantum‐mechanical calculations are increasingly employed when designing new alloys as they accurately predict basic thermodynamic, structural, and functional properties using only the atomic composition as input. We have therefore performed a quantum‐mechanical study using density functional theory (DFT) to systematically explore fundamental physical properties of a broad set of bcc MgLi‐based compounds. These DFT‐determined properties are used to calculate engineering parameters such as (i) the specific Young's modulus (Y/ρ) or (ii) the bulk over shear modulus ratio (B/G) which allow differentiating between brittle and ductile behavior. As we have recently shown, it is not possible to increase both specific Young's modulus, as a measure of strength, and B/G ratio, as a proxy for ductility, by changing only the composition in the binary bcc Mg–Li system. In an attempt to bypass such fundamental materials‐design limitations, a large set of MgLi–X substitutional ternaries derived from stoichiometric MgLi with CsCl structure are studied. Motivated by the fact that for Mg–Li alloys (i) 3rd row Si and Al and (ii) 4th row Zn are industrially used as alloying elements, we probe the alloying performance of the 3rd (Na, Al, Si, P, S, Cl) and 4th row transition metal (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn) elements. The studied solutes offer a variety of properties but none is able to simultaneously improve both specific Young's modulus and ductility. Therefore, in order to explore the alloying performance of yet a broader set of solutes, we predict the bulk modulus of MgX and LiX B2‐compounds running over 40 different elements.     

An organization-wide approach for an effective communication system, Part 2

This is the second article in a two-part series that describes an organization's approach to designing, implementing, and evaluating a communication system. Part 1 of this series, published in the March 1998 issue, focused on the design and implementation of this system. This article addresses the evaluation of outcomes related to identified goals to improve communication flow and decision making on multiple levels and to promote accountability for clinical and operational performance. Implementation strategies involving change management, emergence of issues with related implications, and planned evolution of this system also are discussed for ongoing organizational performance improvement.     

Multistatic Ground-Penetrating Radar Experiments

A multistatic ground-penetrating radar (GPR) system has been developed and used to measure the response of a number of targets to produce data for the investigation of multistatic inversion algorithms. The system consists of a linear array of resistive-vee antennas, microwave switches, a vector network analyzer, and a 3-D positioner, all under computer control. The array has two transmitters and four receivers which provide eight bistatic spacings from 12 to 96 cm in 12-cm increments. Buried targets are scanned with and without surface clutter, which is a layer of rocks whose spacing is empirically chosen to maximize the clutter effect. The measured responses are calibrated so that the direct coupling in the system is removed, and the signal reference point is located at the antenna drive point. Images are formed using a frequency-domain beamforming algorithm that compensates for the phase response of the antennas. Images of targets in air validate the system calibration and the imaging algorithm. Bistatic and multistatic images for the buried targets are very good, and they show the effectiveness of the system and processing.     

An organization-wide approach for an effective communication system, Part 1

This two-part series provides a cogent discussion of designing and implementing an effective communication system, with a committee structure based on the Joint Commission on Accreditation of Health Care Organizations (JCAHO) functions. Part one includes the development and design using a systems approach. Part two, which will be published in the April 1998 issue of JONA, will address the evaluation of outcomes and implications of this communication system. The experiential learning gained from this process is illustrated by the analysis of themes that surfaced during the implementation.