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Synthesis, structures, and unusual solution dynamic processes of d(10) metal complexes of hexakis(3,5-dimethylpyrazolyl)cyclotriphosphazene (L) are reported. Reaction systems with three MX(n):L mole ratios (MX(n) = d(10) metal halide) in CH(2)Cl(2) have resulted in the formation of [ICu(&mgr;,eta(3),eta(3)-L)CuI] (1), [Cl(2)Zn(&mgr;,eta(2),eta(3)-L)ZnCl(2)] (2), [Cl(2)Cd(&mgr;,eta(3),eta(3)-L)CdCl(2)] (3), and [(eta(3)-L)HgCl(2)] (4). These compounds were characterized by single crystal X-ray diffraction studies, and crystallographic data are given in the order of compound: crystal system; space group; unit cell parameters; Z; unique data (I > 2sigma(I)); R(1). 1.0.5CH(2)Cl(2): monoclinic; P2(1)/c; a = 8.268(4) Å; b = 22.365(5) Å; c = 23.325(8) Å, beta = 93.06(1) degrees; 4; 5736; 4.82. 2.CH(3)CN: monoclinic; P2(1)/c; a = 17.021(3) Å; b = 12.161(2) Å; c = 23.608(5) Å; beta = 107.72(1) degrees; 4; 5469; 3.16. 3.CH(2)Cl(2): monoclinic; P2(1)/n; a = 18.585(5) Å; b = 17.585(4) Å; c = 14.404(3) Å; beta = 102.71(2) degrees; 4; 3814; 3.65. The structure of 4 was attempted but resulted in data of low precision. Reaction of L with CuI and ZnCl(2) in an equimolar ratio afforded [ICu(&mgr;,eta(3),eta(3)-L)ZnCl(2)] (5) which crystallizes in monoclinic space group P2(1)/n with a = 22.876(5) Å, b = 21.594(4) Å, c = 9.177(2) Å, beta = 93.54(2) degrees, Z = 4, and R(1) = 7.00 for 3806 (I > 2sigma(I)) data. In all cases, metal halide centers except the Td zinc site in 2 are coordinated by L via a kappa(3)N binding core consisting of two nongeminal pyrazolyl nitrogen atoms and one phosphazene ring nitrogen atom. The eta(2)-N(2) coordination in 2 involves two geminal pyrazolyl nitrogen atoms. Factors which govern the nuclearity of the complex were partially demonstrated. The intermetallic distances in dinuclear metallophosphazenes range from 6.790 to 7.195 Å. The solution behavior of five compounds was studied by variable temperature (31)P{(1)H}, (1)H, and (113)Cd FT NMR spectroscopy. Compounds 1 and 4 are associated with fluxional motions involving A(2)B low-temperature limit spectrum while compounds 2 and 5 show solvent-dependent dynamic processes with ABX and A(2)B low-temperature limit spectral patterns. Compounds 3 constitutes a fluxional system involving three A(2)B species. Accounts of solution NMR spectra were attempted by using PANIC, by assuming the formation of new solution metallophosphazene species and by considering several types of dynamic processes such as a ring-around type hopping motion for the kappa(3)N metal site, a Td conformational change for the geminal pyrazolyl kappa(2)N metal site, and a wigwag motion for the nongeminal pyrazolyl kappa(2)N metal unit.

The ability of heparin to interact with plasma proteins, in particular antithrombin III (ATIII) and thrombin, is its primary mechanism as an anticoagulant drug. Research efforts have focused on the biological activity of heparin under three conditions: in solution as a free molecule, chemically coupled directly onto a polymer surface, and coupled onto a polymer surface using hydrophilic spacer groups. Each of these conditions yields altered biological activity, presumably a result of differing binding interactions with ATIII and thrombin. In this report, insights into binding interaction of direct versus polyethylene oxide space immobilized heparin with ATIII, thrombin, and the generation of the thrombin-antithrombin complex will be presented.

The chemical immobilization of heparin onto polymeric materials through hydrophilic spacer groups was performed to improve the hemocompatibility of blood-contacting devices. Significant data have been gathered attesting to the biological activity of immobilized heparin in static in vitro studies (clotting times) and dynamic in vivo studies (thrombus formation). However, few studies have been performed to investigate the binding kinetics of spacer-immobilized heparin under flow (shear stress) with antithrombin III (ATIII) and thrombin. To help elucidate this binding mechanism, a mathematical model was developed which parallels experiments to measure protein binding and dissociation at the heparin immobilized surface under flow conditions. Heparinized tubing was prepared by chemically immobilizing a high-ATIII-affinity fraction of heparin onto the surface of poly(ethylene)-oxide grafted, poly(styrene-co-p-aminostyrene)-coated polyethylene tubing. ATIII was first bound onto the immobilized heparin, followed by the introduction of thrombin to interact with ATIII. The concentration of thrombin-ATIII complex (TAT) flowing from the tubing was determined, and the dissociation rate constants (kD) of TAT from immobilized heparin were calculated as a function of flow rate. The results indicate that the dissociation rate constant of TAT varied with flow rate, especially low flow rates, high flow rates, and turbulent flow. As the TAT complex dissociates from immobilized heparin, this "recovered" heparin is available for subsequent binding of more ATIII and thrombin. These in vitro mathematical results may help support mechanisms and hypotheses generated for the biological activity of spacer-immobilized heparin observed during long-term in vivo and ex vivo experiments.

We have designed a low-loss single-mode GaAs/AIGaAs optical waveguide with a symmetric five-layer heterostructure at the 1.31-µm wavelength by use of an effective-index method. Waveguides with a W-shaped refractive-index profile have been grown by use of a metallo-organic chemical vapor deposition technique and fabricated with a chemical wet-etching method. Propagation loss has been measured by use of the Fabry-Perot resonance method and a sequential-cleaving experiment. The measured loss is as low as 0.19 dB/cm for waveguides with 2.3-µm thickness and 4.3-µm width, which is comparable to the lowest-loss semiconductor waveguides yet reported. These waveguides could be used to make low-loss modulators for guided-wave devices.

An objective of this research is to verify the mechanism of anticoagulant activity of surface-immobilized heparin in the presence of plasma proteins. The competition and binding interaction between immobilized heparin and antithrombin III (ATIII)/thrombin have been described in vitro. However, the strong ionic character of heparin leads to its specific and nonspecific binding with many other plasma proteins. Most notably, fibronectin contains six active binding sites for heparin which may interfere with the subsequent binding of heparin with ATIII or thrombin. Heparin was covalently immobilized through polyethylene oxide (PEO) hydrophilic spacer groups onto a model surface synthesized by random copolymerization of styrene and p-aminostyrene. The binding interaction of immobilized heparin with ATIII was then determined in the presence of different fibronectin concentrations. The binding interaction was studied by first binding immobilized heparin with ATIII, followed by the introduction of fibronectin; heparin binding with fibronectin, followed by incubation with ATIII, and simultaneous incubation of surface immobilized heparin with ATIII and fibronectin. The extent of ATIII binding to heparin in each experiment was assayed using a chromogenic substrate for ATIII, S-2238. The results of this study demonstrate that the displacement of ATIII from immobilized heparin was proportional to the fibronectin concentration, and was reversible. Furthermore, the binding sequence did not play a role in the final concentration of ATIII bound to immobilized heparin.

The authors previously developed a filter device containing immobilized protamine (termed "protamine filter") that could be used to remove heparin during extracorporeal perfusion. In vivo studies involving dogs showed that the protamine filter removed more than 50% of heparin from the animals' blood circuit in less than 20 min. In addition, the use of the protamine filter did not elicit statistically significant protamine induced hemodynamic and thrombocytopenic responses. Biocompatibility of the protamine filter was also evaluated, with the focus on its effect on the coagulation cascade, the complement system, and the blood antithrombin III levels. Results showed that heparin adsorbed to the protamine coated surface retained 20% of its original activated partial thromboplastin time activity, rendering the coated surface antithrombotic. Activation of the coagulation system by the protamine coated membrane and the untreated cellulose membrane, as measured by the elevation of prothrombin fragment F1 + 2 levels, was statistically identical. The CH50 hemolytic assay showed that the protamine coated membrane produced a reduction of 1.2 +/- 0.8% of the total complement levels, as compared to 9.4 +/- 1.6% by the untreated membrane. In addition, the change in C3a des Arginine levels after 30 min of circulation was 1.5 +/- 0.2 mg/ml by the protamine filter, as compared to 2.1 +/- 0.1 mg/ml by the untreated membrane. Unlike native heparin that would bind with antithrombin, heparin adsorbed on the protamine coated surface was devoid of such activity, and produced no depletion of circulating antithrombin. Because of the limited capacity of the protamine filter, the future system is envisioned to consist of two filters; while one filter is removing heparin the other will be regenerated. With a recently developed heparin sensor, it should be possible to design a sensor directed, biofeedback, two filter heparin removal system.

The immobilization of heparin onto polymeric surfaces using hydrophilic spacer groups has been effective in curtailing surface induced thrombus formation. In this study, the effect of hydrophilic spacers (PEO) on the binding kinetics of immobilized heparin with antithrombin III (ATIII) and thrombin was investigated. Monodispersed, low molecular weight heparin was fractionated on an ATIII affinity column to isolate high-ATIII affinity heparin. This high-ATIII affinity fraction was immobilized onto a styrene/p-amino styrene random copolymer surface using hydrophilic poly(ethylene oxide) (PEO) spacer groups. Styrene/p-amino styrene random copolymer was chosen as the model surface to provide quantitative and reproducible surface concentrations of available amine groups, grafted PEO spacers, and immobilized heparin. The polymer substrate was coated onto glass beads, tolylene diisocyanate modified PEO was covalently coupled to the surface, followed by heparin immobilization. The bioactivity of immobilized heparin was 16.2%, relative to free heparin, and a 1:1 binding ratio between heparin and PEO was achieved. The binding of ATIII and thrombin to control surfaces (no heparin), soluble heparin, heparin immobilized directly onto the surface, and heparin immobilized via spacer groups, were compared. Soluble heparin bound both thrombin and ATIII, while heparin immobilized directly onto the surface bound only thrombin. Spacer-immobilized heparin bound both ATIII and thrombin, although to a lesser extent than soluble heparin. Thus, the enhanced bioactivity of spacer-immobilized heparin, compared to direct-immobilization, may be attributed to the retention of ATIII binding.

The immobilization of heparin onto polymeric surfaces using a hydrophilic spacer was effective in curtailing surface induced thrombus formation. In this study, the binding kinetics of immobilized heparin with antithrombin III (ATIII) and thrombin were investigated. Low molecular weight heparin (molecular weight, 6,000 daltons) was fractionated on an ATIII affinity column, and it was immobilized onto a styrene/p-amino styrene random co-polymer surface via hydrophilic spacer groups. This polymer substrate was coated onto glass beads (diameter range, 0.088-0.105 mm). PEO (molecular weight 3,400), modified by tolylene diisocyanate, was covalently coupled as a spacer group, followed by heparin. The bioactivity of immobilized heparin was approximately 16.2%, relative to free heparin, and nearly 1:1 binding between heparin and PEO was calculated. The binding constants of immobilized heparin and ATIII, and immobilized heparin and thrombin, were 0.958 x 10(7) M-1 and 1.76 x 10(8) M-1, respectively. The immobilized heparin bound with both ATIII and thrombin, and the binding mechanism was similar to that of free heparin.

The living arrangements of disabled elderly people are an important policy-related issue. This investigation focused on testing four models which posit alternative ways in which disability might affect coresidence with adult relatives. The models were tested for a pooled sample of elderly men drawn from the 1976 and 1981 rounds of the National Longitudinal Survey of Mature Men. The methodological strategies for model assessment included descriptive and logistic regression techniques. Men with multiple disabling conditions, but not a single disability, were more likely to be coresiding with adult relatives than were nondisabled men, independent of a set of selected background characteristics. These results provided general support for a model focused on assistance norms. There was some suggestion that the absence of a spouse reinforces this pattern.

A total of 54 patients with major salivary gland tumor were treated with radiation therapy at the University of Michigan from 1955 to 1975, inclusive. Fifteen had total resection and radiation, 16 had subtotal resection and radiation, and 23 were inoperable and received radiation only. Local control rate was different between these groups, 86.7%, 75%, 21.7% respectively, as was survival rate at 5 years, 78.4%, 59.8%, 29.9%. In patients with facial nerve palsy, with combined surgery and radiation, 65.3% local control and 49.7% 5-year survival was obtained. Regional neck node metastasis was noted in 25.5% and distant metastasis in 24.1%. Local tumor control was found to be a very important factor in survival: 70.2% survival in patients with local control and 28.7% without. The authors conclude that a combined radical surgery and postoperative radiation would improve the prognosis of these patients with major salivary gland tumors.