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At least 1,585 records · Page 88Linked to original sources
PubMed1995

The pharmacokinetics of subcutaneously administered recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis: relation to parameters of the acute-phase response. The ALS CNTF Treatment Study (ACTS) Phase I-II Study Group.

Fifty-seven patients with amyotrophic lateral sclerosis (ALS) were randomly assigned to receive single subcutaneous doses of 0.5, 1, 3, 7, 10, or 30 micrograms/kg recombinant human ciliary neurotrophic factor (rHCNTF) or placebo. Peak plasma concentrations occurred 180 to 260 min after dosing. rHCNTF plasma concentrations then appeared to decay, with an apparent elimination half-life of 120-400 min. Eight of 12 patients who received the highest dose had measurable plasma rHCNTF levels 24 h after dosing. Peak plasma concentrations of rHCNTF in patients receiving 30 micrograms/kg rHCNTF were in the range that has been shown to support the survival of embryonic rat and human motor neurons in tissue culture. Systemic exposure to rHCNTF increased with increasing dose. The elimination of rHCNTF, over the dose range evaluated, appeared to follow first-order processes. Elevations in body temperature and evidence of activation of the acute phase response were observed.

Adult↗
PubMed2004

Role of the thymus in transplantation tolerance in miniature Swine: IV. The thymus is required during the induction phase, but not the maintenance phase, of renal allograft tolerance.

BACKGROUND: The authors' laboratory previously demonstrated that long-term tolerance to class I-disparate renal allografts in miniature swine can be induced by a short course of cyclosporine A (CsA), and that this stable tolerance is dependent on the presence of an intact thymus. In the present study, the authors have examined the requirement for a thymus during the pretransplant, induction, and maintenance phases of tolerance. METHODS: Twenty-two miniature swine underwent class I major histocompatibility complex-mismatched renal transplantation, with a 12-day course of CsA. Thymectomies were performed on days -21, 0, +8, +21, and greater than or equal to +42, in relation to the day of transplantation. Historical controls consisted of euthymic and sham-thymectomized recipients. RESULTS: Euthymic, sham-thymectomized, and day-greater than or equal to +42 thymectomized recipients demonstrated stable renal function and minimal anti-donor cytotoxic T-lymphocyte (CTL) responses. In contrast, day -21 and day 0 thymectomized recipients demonstrated allograft dysfunction, marked cellular infiltrates, with severe vasculitis and glomerular changes, and strong anti-donor CTL responses. Animals thymectomized on days +8 and +21 did not undergo severe rejection, but likewise did not demonstrate a stable clinical course. CONCLUSIONS: These data indicate that the requirement for thymic function in the induction of rapid and stable tolerance is greatest during the first 8 days and then diminishes over the next 2 weeks posttransplant. Failure of thymectomy to affect the course of tolerance after day +21 suggests that thymic function is not required for the maintenance of tolerance. Understanding the role of the thymus in establishing tolerance may permit the development of tolerance induction strategies, especially for pediatric transplant recipients.

Animals↗
PubMed2003

Towards a quantitative phase-field model of two-phase solidification.

We construct a diffuse-interface model of two-phase solidification that quantitatively reproduces the classic free boundary problem on solid-liquid interfaces in the thin-interface limit. Convergence tests and comparisons with boundary integral simulations of eutectic growth show good accuracy for steady-state lamellae, but the results for limit cycles depend on the interface thickness through the trijunction behavior. This raises the fundamental issue of diffuse multiple-junction dynamics.

Journal Article↗
PubMed2000

New phase and surface melting of Si(111) at high temperature above the (7x7)-(1x1) phase transition

The surface structure of Si(111) at high temperatures (950-1380 degrees C) has been studied with reflection high-energy electron diffraction. We have found three different surface structures: (1) A relaxed bulklike structure with adatoms of 0.25 monolayer (ML) is formed (950-1210 degrees C); (2) there is a new phase where the adatom coverage decreases to 0.20 ML (1250-1270 degrees C); (3) the surface melting occurs over 1290 degrees C. The crystalline structure below the melting layer can be explained by the vacancy model missing all adatoms and 0.45 ML of atoms in the first-double layer.

Journal Article↗
PubMed2002

Smectic phases with cubic symmetry: the splay analog of the blue phase.

We report on a construction for smectic blue phases, which have quasi-long-range smectic translational order as well as long-range cubic or hexagonal order. Our proposed structures fill space with a combination of minimal surface patches and cylindrical tubes. We find that for the right range of material parameters, the favorable saddle-splay energy of these structures can stabilize them against uniform layered structures.

Journal Article↗
PubMed2005

Surface-assisted monodomain formation of an ordered phase of soft matter via the first-order phase transition.

We produced a monodomain ordered structure with the help of a surface-mediated first-order transition, using a sponge-to-lamella transition in a membrane suspension as a model system. The long characteristic length and time scales of the system allow us to observe the process of the phase ordering in a confined geometry with optical microscopy in real time. We demonstrate that a homogeneously ordered domain can be attained if we prevent nucleation in bulk by using its kinetic coupling to nucleation on the surface.

Journal Article↗
PubMed2001

Ferroelectric--paraelectric phase transitions with no group--supergroup relation between the space groups of both phases?

The structures of Sr(3)(FeF(6))(2), beta-NbO(2), TlBO(2) and CrOF(3), previously reported as possible ferroelectrics with no group-supergroup relation between the ferroelectric and the paraelectric symmetries, have been carefully studied. We could not confirm any structural pseudosymmetry with respect to a space group which is not a supergroup of their room-temperature polar space group. In all cases, pseudosymmetry was indeed detected, but only for non-polar supergroups of the actual space groups of the structures. In this sense, the four compounds are possible ferroelectrics, but fulfilling the usual group-supergroup relation between the phase symmetries.

Journal Article↗
PubMed1995

The effect of matrix phase morphology on the structure of Ag-Cu-Pd dispersed phase dental amalgam.

The effect of an Ag-Cu-Pd dispersant alloy on the structure of amalgams fabricated with two different particle types of low-copper amalgam matrices was investigated. In amalgams L and L (0), a low-copper lathe-cut amalgam Aristalloy was used as the matrix. In amalgams S and S(0), the matrix used was Spheralloy, a low-copper spherical amalgam. X-ray diffraction was used to analyse the relative content of the phases in the amalgams. The presence of Pd in the dispersant of amalgams L and S resulted in a decrease in the amount of eta' (Cu6Sn5) and an increase in the amount of unreacted particles when compared to the controls L(0) and S(0). Amalgams fabricated with a spherical alloy matrix (S and S(0)) showed a greater effect than amalgams fabricated with a lathe-cut matrix alloy (L and L(0)).

Chemical Phenomena↗
PubMed1996

Phase I and phase II enzymes produced by Cunninghamella elegans for the metabolism of xenobiotics.

The filamentous fungus Cunninghamella elegans has the ability to metabolize xenobiotics, including polycyclic aromatic hydrocarbons and pharmaceutical drugs, by both phase I and II biotransformations. Cytosolic and microsomal fractions were assayed for activities of cytochrome P450 monooxygenase, aryl sulfotransferase, glutathione S-transferase, UDP-glucurono-syltransferase, UDP-glucosyltransferase, and N-acetyltransferase. The cytosolic preparations contained activities of an aryl sulfotransferase (15.0 nmol min-1 mg-1), UDP-glucosyltransferase (0.27 nmol min-1 mg-1) and glutathione S-transferase (20.8 nmol min-1 mg-1). In contrast, the microsomal preparations contained cytochrome P450 monooxygenase activities for aromatic hydroxylation (0.15 nmol min-1 mg-1) and N-demethylation (0.17 nmol min-1 mg-1) of cyclobenzaprine. UDP-glucuronosyltransferase activity was detected in both the cytosol (0.09 nmol min-1 mg-1) and the microsomes (0.13 nmol min-1 mg-1). N-Acetyltransferase was not detected. The results from these experiments provide enzymatic mechanism data to support earlier studies and further indicate that C. elegans has a broad physiological versatility in the metabolism of xenobiotics.

Biotransformation↗
PubMed2006

Contrasting changes in phase I and phase II metabolism of acetaminophen in male mice pretreated with carbon tetrachloride.

Effect of carbon tetrachloride (CCl(4)) pretreatment on the biotransformation and elimination of acetaminophen were examined in male mice. A 24 hr initial dose of CCl(4) (0.05 ml/kg, intraperitioneally) reduced the induction of hepatotoxicity resulting from acetaminophen treatment (350 mg/kg, intraperitoneally) as determined by changes in serum alanine and aspartate aminotransferase, and sorbitol dehydrogenase activities. Acetaminophen and the major metabolites in plasma were monitored for 12 hr following acetaminophen treatment. CCl(4) pretreatment decreased the plasma concentrations of acetaminophen-cysteine and acetaminophen-mercapturate, but acetaminophen-glucuronide and acetaminophen-sulfate were increased significantly. The elimination of the parent drug from plasma was not affected by CCl(4). In urine collected for 24 hr, the concentrations of acetaminophen-sulfate and acetaminophen-glucuronide were increased by 84% and 33%, respectively, whilst acetaminophen-cysteine and acetaminophen-mercapturate were reduced to approximately one third of control. Expression of cytochrome P450 (CYP) isozymes was determined using antibodies of 2E1 and 1A2 as probes. CYP2E1 and 1A2 expressions were decreased significantly by CCl(4). Likewise, CCl(4) treatment reduced the microsomal p-nitrophenol hydroxylase and p-nitroanisole O-demethylase activities to less than one third of control. The results indicate that, although CCl(4) reduces the generation of thioether conjugates of acetaminophen by decreasing the CYP activities, inhibition of the oxidative metabolism of acetaminophen is counterbalanced by the enhancement of conjugate formation via the glucuronide and sulfate pathways, resulting in elimination of the drug at a rate equivalent to that in normal mice. It is suggested that liver injury in patients may not warrant a mandatory reduction of drug doses extensively inactivated via phase II reactions.

Acetaminophen↗
PubMed2006

Energetics and surface properties of Pseudomonas putida DOT-T1E in a two-phase fermentation system with 1-decanol as second phase.

The solvent-tolerant strain Pseudomonas putida DOT-T1E was grown in batch fermentations in a 5-liter bioreactor in the presence and absence of 10% (vol/vol) of the organic solvent 1-decanol. The growth behavior and cellular energetics, such as the cellular ATP content and the energy charge, as well as the cell surface hydrophobicity and charge, were measured in cells growing in the presence and absence of 1-decanol. Although the cells growing in the presence of 1-decanol showed an about 10% reduced growth rate and a 48% reduced growth yield, no significant differences were measured either in the ATP and potassium contents or in the energy charge, indicating that the cells adapted completely at the levels of membrane permeability and energetics. Although the bacteria needed additional energy for adaptation to the presence of the solvent, they were able to maintain or activate electron transport phosphorylation, allowing homeostasis of the ATP level and energy charge in the presence of the solvent, at the price of a reduced growth yield. On the other hand, significantly enhanced cell hydrophobicities and more negative cell surface charges were observed in cells grown in the presence of 1-decanol. Both reactions occurred within about 10 min after the addition of the solvent and were significantly different after killing of the cells with toxic concentrations of HgCl2. This adaptation of the surface properties of the bacterium to the presence of solvents seems to be very similar to previously observed reactions on the level of lipopolysaccharides, with which bacteria adapt to environmental stresses, such as heat shock, antibiotics, or low oxygen content. The results give clear physiological indications that the process with P. putida DOT-T1E as the biocatalyst and 1-decanol as the solvent is a stable system for two-phase biotransformations that will allow the production of fine chemicals in economically sound amounts.

Adenosine Triphosphate↗
PubMed1994

Carcinoma of the prostate gland: MR imaging with pelvic phased-array coils versus integrated endorectal--pelvic phased-array coils.

PURPOSE: To compare the performance of pelvic phased-array (PPA) coils and integrated endorectal PPA coils in evaluation of local extent of prostate cancer. MATERIALS AND METHODS: Seventy-one men underwent magnetic resonance (MR) imaging within 3 weeks of radical prostatectomy. MR findings of tumor, extracapsular extension, seminal vesicle invasion, nodal involvement, and stage were compared with step-sectioned (3-4-mm intervals) whole-mounted pathologic specimens. Prospective consensus versus single-reader interpretation (kappa statistics) and PPA versus integrated endorectal PPA coils (McNemar test) were compared, and a rating scale of 1-6 was developed for analysis of receiver operating characteristics. Statistical significance was calculated at delta = .05. RESULTS: Comparison between consensus and single-reader image interpretation showed positive but poor agreement (kappa = .38) and no statistical significance. Staging accuracy was better (difference approached significance) for integrated endorectal PPA coils (77%) than for PPA coils (68%). CONCLUSION: The integrated endorectal PPA coil is better for evaluation of local prostatic cancer than is the PPA coil.

Humans↗
PubMed1990

Tumor necrosis factor in advanced colorectal cancer: a phase II study. A trial of the phase I/II study group of the Association for Medical Oncology of the German Cancer Society.

In a phase II study, the efficacy and toxicity of human recombinant tumor necrosis factor (rh TNF-alpha) were evaluated in patients with advanced colorectal carcinoma. Rh TNF-alpha was given as short term infusion at a dose of 3 x 10(5) U/m2 on three successive days. Treatment was repeated after a two week interval. The response was evaluated after four treatment cycles. In 15 patients entering the study, we found one partial response, one stable disease, 9 progressive diseases, and four patients who were not evaluable for tumor remission. There were numerous side effects of the treatment, mainly fever, chills, loss of appetite, leukopenia, and hepatotoxicity. In this regimen, rh TNF-alpha does not suggest a therapeutic advantage for treatment of advanced colorectal carcinoma.

Adenocarcinoma↗
PubMed2001

Facile solid-phase synthesis of sulfated tyrosine-containing peptides: Part II. Total synthesis of human big gastrin-II and its C-terminal glycine-extended peptide (G34-Gly sulfate) by the solid-phase segment condensation approach.

Application of the fluoren-9-ylmethoxycarbonyl (Fmoc)-based solid-phase segment condensation approach to the preparation of sulfated peptides was investigated through the synthesis of human big gastrin-II, a 34-residue sulfated tyrosine [Tyr(SO3H)]-containing peptide. Highly acid-sensitive 2-chlorotrityl resin (Clt resin) was exclusively employed as an anchor-resin for the preparation of the three peptide segments having the C-terminal Pro residue as well as of the Tyr(SO3H)-containing resin-bound segment. By using the PyBOP-mediated coupling protocol [PyBOP=benzotriazolyloxytris(pyrrolidino)phosphonium hexafluorophosphatel, we successively condensed each segment and constructed the 34-residue peptide-resin without any difficulty. The final acid treatment of the fully protected peptide-resin at low temperature (90% aqueous TFA, 0 degree C for 8 h), which can detach a Tyr(SO3H)-containing peptide from the resin and remove the protecting groups concurrently with minimum deterioration of the sulfate, afforded a crude sulfated peptide. After one-step HPLC purification, a highly homogeneous human big gastrin-II was easily obtained in 14% yield from the protected peptide-resin. The sulfate form of the C-terminal glycine-extended gastrin (G34-Gly sulfate), a posttranslational processing intermediate of gastrin-II, was also successfully prepared with the segment condensation approach (11% yield). These results demonstrated the usefulness of the segment condensation protocol for preparing large Tyr(SO3H)-containing peptides.

Gastrins↗
PubMed2003

Encoding amplitude and phase information onto a binary phase-only spatial light modulator.

We report what to our knowledge is a new technique for encoding both amplitude and phase information onto a single binary-valued spatial light modulator. In our approach, we spatially modulate the diffraction efficiency of the filter. Light that is not diffracted into the first order is sent into the zero order, effectively allowing amplitude modulation of either the first-order or zero-order diffracted light. This technique has applications in both optical pattern recognition and image processing. Experimental results are included.

Journal Article↗
PubMed2004

Effect of phase imperfections on high-order mode selection with intracavity phase elements.

To obtain a laser beam containing only one pure high-order transverse mode, one can insert a binary phase element (BPE) into a laser resonator. I investigate the effect of deviations in the discontinuous height of the BPE on the selection of high-order Hermite-Gaussian (HG) modes. Both matrix-diagonalization and numerical Fox-Li calculations to obtain the loss per pass and beam propagation factor of the output beam obtained with a deviated BPE are performed. Experimental results obtained with a Nd:YAG laser operated with HG (1,0) and HG (1,1) transverse modes are presented and compared with theoretical modes.

Journal Article↗
PubMed2000

Characterization of SNP, a novel tissue- and phase-specific nuclear protein expressed during the proliferative phase in the oviduct of the lizard Podarcis sicula Raf.

The amino acid sequence of a novel tissue-and phase-specific nuclear protein (SNP) has been determined, after purification from the nuclei of the oviduct of the lizard Podarcis sicula Raf. during the reproductive period of the seasonal growth. SNP has a pI of 9.0 and contains 81 amino acid residues with a molecular weight of 9211.88 +/- 0.09. It shows a bipartite organization as the first 40 amino acids contain all 8 cysteinyl residues, while the last 41 amino acids contain 16 prolyl residues. Two more components have also been identified and characterized, with the first 79 amino acids matching SNP and missing one or two residues at the C-terminus. They have thus been named [des-(Ala81) SNP1] and [des-(Lys80-Ala81) SNP2], respectively. The molecular weights are 9140.21 +/- 0.83 for [des-(Ala81) SNP1] and 9011 +/- 0.09 for [des-(Lys80-Ala81) SNP2].

Amino Acid Sequence↗
PubMed1983

Immobilisation of antibodies and antigens on macro solid phases--a comparison between adsorptive and covalent binding. A critical study of macro solid phases for use in immunoassay systems. Part I.

This article describes a comparison between adsorption and covalent binding of protein-conjugates (bovine serum albumin-diazoluminol), antibodies (sheep anti-human thyrotropin) and haptens ([125]thyroxine) to polystyrene, nylon and glass balls. Different combinations of adsorption and covalent binding were used; these varying with the solid phase in question. Polystyrene balls were preactivated by adsorption of a copolymer of phenylalanine and lysine (poly phe-lys) from aqueous solution. The treated balls were then in most cases chemically activated with pentane-1,5-dial before coupling the substance under test. Polystyrene balls were directly chemically activated by nitration followed by reduction and diazotisation. Nylon balls were either used as received or partially hydrolysed with either hydrochloride acid or sodium hydroxide before further use. Chemical activation was carried out using either carbodiimides or pentane-1,5-dial, the latter proving to be unsuitable because of cross-linking between amino groups on the ball surface. Glass balls were coated with organofunctional aminosilanes followed by chemical activation with pentane-1,5-dial. The best results were obtained using nylon balls activated with carbodiimides and with polystyrene balls coated with poly phe-lys and chemically activated with pentane-1,5-dial. Glass balls proved to be unsuitable as the coating precision was poor under laboratory conditions.

Adsorption↗