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Bioaccumulation of yttrium in Pseudomonas fluorescens and the role of the outer membrane component(s).

Pseudomonas fluorescens was grown in millimolar amounts of yttrium. The tolerance to yttrium appeared to be mediated by the ability of the organism to accumulate the trivalent metal predominantly in the outer membrane component(s). At the stationary phase of growth, 65 to 70% of the metal was associated with the constituent(s) of the outer membrane. Treatment with 2 mM (EDTA) did not release the metal. Incubation of the outer membrane fraction with yttrium led to further accumulation of the metal. The outer membrane equivalent to 1 mg of protein was shown to immobilize 175 microg of yttrium. There was no significant variation in uronic acid and the lipid contents of the control and yttrium-stressed cells as monitored by colorimetric assays. The protein profiles of the outer and inner membrane components obtained from the control and metal-stressed cells showed marked variations as revealed by sodium dodecyl sulphate polyacrylamide gel electrophoretic analysis.

Bacterial Outer Membrane Proteins↗

Recurrent villonodular synovitis of the knee. Successful treatment with yttrium-90.

A 40-year-old woman with recurrent pigmented villonodular synovitis of the knee was treated with Yttrium-90 radiocolloid. The advantages of Yttrium-90 include effectiveness, low cost, simplicity, and low morbidity. The radiophysical properties of Yttrium-90 that make it a useful therapeutic agent are short half-life, pure beta emission and good penetration of the soft tissues. Side effects are few, predictable, and for the most part, avoidable. Radionecrosis of soft tissue, needle tract pigmentation, injection site tenderness, pyrexia, and lymphocyte chromosomal abnormalities have been reported. The indications for intra-articular radiocolloid therapy are the same as for surgical synovectomy, except that it is reserved for patients older than 35 years of age. The pathologic events following Yttrium-90 therapy in experimental animals show coagulation necrosis of the synovium, followed by an intense inflammatory reaction, leading ultimately to fibrosis. Yttrium-90 is a useful adjuvant in the treatment of recurrent pigmented villonodular synovitis.

Biopsy↗

[Hygienic regulation of yttrium, terbium, ytterbium and lutetium fluorides in the air of the workplace].

The study (experiments on animals and on culture of rats' peritoneal macrophages) covered fluorides of rare-earth metals (REM) assigned to yttrium group--yttrium, terbium, ytterbium, lutetium. Fluorides of REM have low toxicity and cumulativity, induce no local irritation of skin and eyes. Fluorides of yttrium, terbium and lutetium, if administered into stomach, result in specific intoxication (fluorosis). Fluoride of ytterbium did not cause such intoxication. According to short-term tests of cytotoxicity, the foreseeable fibrogenic danger for ytterbium fluoride is moderate, for fluorides of yttrium, terbium and lutetium is mild. The authors recommend to control the level of yttrium, terbium and lutetium fluorides in the air of workplace through the MACs for the fluorides at 2.5 mg/cu m (maximal single concentration) and 0.5 mg/cu m (average shift concentration), the level of ytterbium fluoride as moderate fibrogenic dust at 6 mg/cu m.

Air Pollutants, Occupational↗

Recurrence of Hodgkin's disease after indium-111 and yttrium-90 labeled antiferritin administration.

BACKGROUND: Indium-111 labeled antiferritin targets 95% of all Hodgkin's disease lesions with a diameter of 1 cm or more. Subsequent treatment with yttrium-90 labeled antiferritin secures a high response rate in patients with recurrent Hodgkin's disease. METHODS: A total of 87 patients were entered on one of three different yttrium-90 labeled antiferritin protocols. Recurrences after yttrium-90 treatment were analyzed. Nine patients were retreated with involved external beam radiation fields, selected with the help of indium-111 labeled antiferritin. RESULTS: In single-agent yttrium-90 antiferritin studies, a response rate of more than 60% was found, with an average response duration of 6 months. One-third of the patients had recurrences in previously uninvolved areas. Repeat indium antiferritin scintigraphy allowed for the selection of new radiation fields for recurrences. In-field disease control was obtained for a median of 8 months, but new recurrences in new areas occurred. Chemotherapy or radiation therapy given immediately before antiferritin decreased tumor targeting with indium-111 labeled antiferritin. CONCLUSIONS: Recurrences after radiolabeled antiferritin treatment are not due to radioresistant Hodgkin's disease. In contrast, Hodgkin's disease less than 1 cm in diameter is not targeted and not controlled by radiolabeled antiferritin. New multimodality regimens with a higher therapeutic ratio are needed for treatment of Hodgkin's disease with curative intent. Radiolabeled antiferritin can be incorporated in such regimens to secure better control of bulky Hodgkin's disease (>1 cm in diameter), but it should be given before chemotherapy or radiation therapy.

Ferritins↗

Tolerance of the liver to the effects of Yttrium-90 radiation.

There are no reliable data documenting the tolerance of the human liver to ionizing radiation from a continuous Yttrium-90 source. As Yttrium-90 incorporated into microspheres is being used to treat patients with liver cancer, it is imperative that the tolerance of the human liver to this form of radiation damage be determined. Four patients with metastatic liver cancer were treated with Yttrium-90 to deliver radiation doses above that considered tolerable when given by conventional external sources. Patients were monitored with serial estimations of liver function tests and between 7 and 9 months after treatment liver biopsies were performed. Histological examination of the liver biopsies confirmed only minimal changes in the normal liver parenchyma. These data indicate that the human liver may tolerate relatively large radiation doses when delivered by Yttrium-90 microspheres embedded in the liver parenchyma as a number of discrete point sources.

Adenocarcinoma↗

Spectrophotometric studies and applications for the determination of yttrium in pure and in nickel base alloys.

Yttrium reacts with 5-(4'-chlorophenylazo)-6-hydroxypyrimidine-2,4-dione (I), 5-(2'-bromophenylazo)-6-hydroxypyrimidine-2,4-dione (II), 5-(2',4'-dimethylphenylazo)-6-hydroxypyrimidine-2,4-dione (III), 5-(4'-nitro-2',6'-dichlorophenylazo)-6-hydroxypyrimidine-2,4-dione (IV), 5-(2'-methyl-4'-hydroxyphenylazo)-6-hydroxypyrimidine-2,4-dione (V) to form a dark pink complexes, having an absorption maximum at 610, 577, 596, 567 and 585 nm, respectively. The complex formation was completed spontaneously in theil buffer solution and the resulting complex was stable for at least 3 h after dilution. Under the optimum conditions employed, the molar absorptivities were found to be 1.60 x 10(4), 1.29 x 10(4), 1.96 x 10(4), 1.45 x 10(4) and 1.21 x 10(4) l mol(-1) cm(-1) and the molar ratios were (1:1) and (1:2) (M:L). The linear ranges were found within 95 microg of yttrium in 25 ml solution. One of the characteristics of the complex was its high tolerance for calcium and hence a method of separation and enrichment of microamounts of yttrium by using calcium oxalate precipitate was developed and applied to measure yttrium in nickel-base alloys. Interfering species and their elimination have been studied. The precision and recovery are both satisfactory.

Alloys↗

Survival of patients with resistant Hodgkin's disease after polyclonal yttrium 90-labeled antiferritin treatment.

PURPOSE: A follow-up study was initiated of patients with Hodgkin's disease who were treated with yttrium 90-labeled antiferritin. Prescription method, pharmacokinetics, acute and late side effects, and survival were evaluated. METHODS: Patients had measurable disease and failed > or = two multiagent chemotherapy regimens previously (N = 44). All patients received 5-mCi indium 111-labeled antiferritin 2 mg intravenously and were scanned repeatedly by gamma camera. In five patients, polyclonal antiferritin (rabbit, pig, or baboon) failed to target the tumor. Thirty-nine patients were injected intravenously with 10-, 20-, 30-, 40-, or 50-mCi yttrium 90-labeled antiferritin 2 to 5 mg. Patients received between one and five cycles. Some patients were supported with 5 x 10(7) autologous bone marrow cells per kilogram. RESULTS: Yttrium 90-labeled polyclonal antiferritin does not produce immunologic, pharmacologic, or microbiologic complications in vivo. Bone marrow toxicity is the only side effect observed. Overall response rate is 20 of 39, or 51%. Two patients had stable disease. A significant positive correlation is found between blood radioactivity level 1 hour after radioimmunoconjugate administration and subsequent response of Hodgkin's disease. A dosage in millicuries per kilogram provides a higher positive correlation with blood radioactivity levels 1 hour after administration than a dosage in millicuries per square meter of body-surface area or in total millicuries. Fifty percent of patients survive for > or = 6 months. CONCLUSION: The low-dose protein used (2 to 5 mg) indicates that the high response rate is due to radiation and not to immunologic effects of the antibody. High-activity administrations followed by bone marrow transplantation are not required for tumor response. The therapeutic ratio of radiolabeled antiferritin is higher than the therapeutic ratio observed in most phase I studies of chemotherapeutic agents. This analysis does not identify a superior mode of treatment for patients with end-stage Hodgkin's disease. However, in a heavily pretreated patient population, prolonged survival is observed after relatively inexpensive treatment. Preclinical research with yttrium 90-labeled antiferritin indicates that significant increases in tumor dose can be obtained in the future without an increase in normal tissue toxicity.

Adolescent↗

Comparison of the erbium-yttrium aluminum garnet and carbon dioxide lasers for in vitro bone and cartilage ablation.

The in vitro bone- and cartilage-ablation characteristics of the solid-state erbium:yttrium aluminum garnet laser were compared to those of the carbon dioxide laser. Ablations of fresh, frozen cadaver septal cartilage and maxillary sinus bone were performed using total energies between 1 and 6 J. Specimens were studied using hematoxylin and eosin stain and digitized, computer-assisted measurements of 35-mm photographs. Erbium-yttrium aluminum garnet-ablated bone averaged 5 microns of adjacent tissue thermal injury, compared with 67 microns with carbon dioxide-ablated bone. Erbium-yttrium aluminum garnet-ablated cartilage averaged 2 microns of adjacent tissue thermal injury, compared with 21 microns with the carbon dioxide-ablated cartilage. The tissue-ablation characteristics of the erbium-yttrium aluminum garnet laser are promising for future otolaryngologic applications.

Aluminum↗

Yttrium-90-ibritumomab tiuxetan radioimmunotherapy: a new treatment approach for B-cell non-Hodgkin's lymphoma.

This article will review the clinical development of ibritumomab tiuxetan, a yttrium-90-conjugated monoclonal antibody to CD20, for patients with relapsed B-cell non-Hodgkin's lymphomas. Ibritumomab is the murine parent anti-CD20 antibody that was engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA chelator that is linked to ibritumomab to form ibritumomab tiuxetan. Since yttrium-90 ((90)Y) is a pure beta emitter and cannot be used for patient imaging, indium-111 ((111)In) is chelated to ibritumomab tiuxetan for tumor and normal organ imaging in clinical practice and for dosimetry in clinical trials. (90)Y-ibritumomab tiuxetan is the form used for therapy. This review discusses the clinical trials that have demonstrated the efficacy of ibritumomab tiuxetan and summarizes the safety data in patients with relapsed B-cell non-Hodgkin's lymphomas. Two phase I trials of (90)Y-ibritumomab tiuxetan were conducted to establish the toxicity profile and the maximum tolerated single dose that could be administered to outpatients without the use of stem cells or prophylactic growth factors. In the first trial, cold ibritumomab was used prior to ibritumomab tiuxetan; the second trial used the human chimeric antibody rituximab. The phase I trials determined that in patients with a platelet count of greater than or equal to 150 x 10(9)/l, a schedule of intravenous rituximab 250 mg/m(2) on days 1 and 8, and 0.4 mCi/ kg of intravenous (90)Y-ibritumomab tiuxetan on day 8 was safe and efficacious and did not require stem cells. A dose of 0.3 mCi/kg was recommended for patients with a baseline platelet count of 100,000- 149,000 x 10(6)/l. Adverse events were primarily hematologic, and nonhematologic adverse events were primarily due to rituximab. There was no normal organ toxicity. The overall response rate was 67% for all patients and 82% in patients with low-grade non-Hodgkin's lymphomas. A subsequent phase III trial randomized 143 eligible patients to either rituximab or ibritumomab tiuxetan. The aim was to demonstrate that the addition of the yttrium-90 radioisotope to the antibody provided additional efficacy over the unconjugated ("cold") rituximab alone. The results of this study showed an overall response rate of 80% with (90)Y-ibritumomab tiuxetan versus 56% for rituximab (p = 0.002). An additional trial enrolled 54 patients who were nonresponsive or refractory to rituximab and treated the patients with a single dose of 0.4 mCi/kg (90)Y-ibritumomab tiuxetan. An overall response rate of 74% was found in these rituximab-refractory patients. These data provide further evidence of the added value of the yttrium-90. Finally, a fifth trial treated 30 patients with mild thrombocytopenia using 0.3 mCi/kg (90)Y-ibritumomab tiuxetan and found an overall response rate of 83%. (90)Y-ibritumomab tiuxetan radioimmunotherapy is a new treatment modality for patients with relapsed B-cell non-Hodgkin's lymphoma. The advantages of this therapy are that it utilizes targeted radiation in a single-dose, outpatient schedule that is well tolerated and accepted by the patient. Future trials will build on these results and determine at what point in the disease course this modality can best be utilized to maximize the benefits to the patient.

Antibodies, Monoclonal↗

[Studies on effects of yttrium chloride and praseodymium chloride on frequency of micronucleus in human blood lymphocytes].

OBJECTIVE: To explore genotoxicity of rare-earth elements, yttrium and praseodymium. METHODS: Effects of yttrium chloride and praseodymium chloride on human lymphocytes cultured in vitro were studied by micronucleus test. RESULTS: Frequency of micronucleus in human blood lymphocytes increased significantly by treatment with yttrium chloride and praseodymium chloride, and it increased with the concentration of the both agents, to a certain range. CONCLUSION: It suggests that rare-earth elements yttrium and praseodymium have certain genotoxicity.

Cells, Cultured↗

Biological dosimetry after yttrium-90 citrate colloid radiosynoviorthesis.

UNLABELLED: Radiosynoviorthesis (RSO) with the ss-particle-emitting nuclide yttrium-90 is an established concept for the treatment of persistent synovitis of the knee joint. The AIM of this study was to investigate the biological radiation effect on the basis of a characteristic radiation parameter. PATIENTS, METHODS: After RSO procedures with yttrium-90 citrate colloid and subsequent immobilisation of the knee, blood specimens of 10 patients were collected immediately before RSO and 11 to 13 days after the intervention. The yield of dicentric chromosomes in the lymphocytes was determined exclusively in metaphases of the first cell cycle in vitro. In addition, activity leakage was measured by wholebody bremsstrahlung-scintigraphy. RESULTS: No statistically significant increase in the number of dicentric chromosomes (26 before treatment and 34 after treatment) in 20 192 cells analyzed from the 20 blood samples could be found as a result of RSO. However, the analysis of at least 1000 cells per blood sample demonstrates a tendency for a biological radiation effect in the blood of patients on the basis of this characteristic radiation parameter. Two of the 10 RSO patients had undergone a second RSO using yttrium-90 citrate, whereby one patient displayed activity transport out of the knee joint, amounting to 6 MBq. Only for him a radiation effect (about 130 mGy per single RSO) could be calculated by biological dosimetry. CONCLUSION: Since in general, based on the analysis of dicentric chromosomes in at least 1000 lymphocytes per individual, detection limits for groups of persons after long-term exposures to low-LET radiation of 50-100 mGy are possible, we assume that RSO with yttrium-90 should be associated with a low whole-body radiation exposure.

Adult↗

[Scintigraphic studies of gonadal burden in radiosynoviortheses of the knee joint with yttrium 90].

Yttrium-90 radiosynoviorthesis of the knee joint in rheumatic inflammatory diseases shows favourable results. Because of the supposed exposure of the patients gonads, Yttrium synoviorthesis has rarely been performed in patients below the age of 40. Scintigraphic studies in 20 patients with rheumatoid arthritis showed no significant leakage of the radionuclide from the knee joint. Gamma camera measurements both phantom and in vivo in the regions of ovary and testes revealed a local dose of 1.05 microGy/MBq (3.9 mrd/mCi) or 1.1 microGy/MBq (4.1 mrd/mCi) of the injected radioactivity. Calculation of the maximum possible load of the gonads, supposing even total leakage of the injected 90-Yttrium from the knee joint, yielded a maximum possible dose of 6 mGy (600 mrd). We conclude from these studies and calculations that Yttrium-90 synoviorthesis of the knee joint can safely be carried out in patients below the age of 40.

Adult↗

[Radiosynoviorthesis with yttrium-90-silicate. Results compared to aurum-198-colloid and whole body radiation load].

The results of the radiosynoviorthesis with yttrium-90 silicate in 36 joints, are reported. In comparison to the radiogold therapy in 64 joint, yttrium-90 was a little more effective. Additionally, the body distribution of radioactive yttrium after radiosynoviorthesis of knee joints, was measured in 6 patients. It could be shown that the uptake of the regional lymphnodes was between 4 and 5% of the yttrium administered. The radiation dose of the regional lymphnodes certainly exceeds 1000 rad. The results point to the importance of a careful selection of patients for radiosynoviorthesis.

Arthritis, Rheumatoid↗

Donor-functionalized lanthanide terphenyl complexes: Synthesis and structural characterization of 2,6-di(o-anisol)phenyl compounds of ytterbium, yttrium, and samarium.

The syntheses and molecular structures of a number of 2,6-di(o-anisol)phenyl ([double bond]Danip-) -based bis(amide) and bis(alkoxide) compounds of ytterbium, yttrium, and samarium are reported. Additionally, NMR spectroscopic data are reported for the analogous diamagnetic yttrium compounds. Salt metathesis reaction of equimolar amounts of DanipLi and YbCl(3) in tetrahydrofuran at room temperature followed by addition of 2 equiv of KN(SiMe(3))(2) or KN(SiHMe(2))(2) produces DanipYb[N(SiMe(3))(2)](2) (1) and DanipYb[N(SiHMe(2))(2)](2) (2), respectively. The analogous reaction using SmCl(3) and KN(SiHMe(2))(2) produces DanipSm[N(SiHMe(2))(2)](2) (3). Reaction of DanipLi and YbCl(3) in tetrahydrofuran at room temperature followed by addition of 2 equiv of KO(2,6-diisopropylphenyl) produces DanipYb[O(2,6-diisopropylphenyl)](2) (4). Our attempts to also prepare the yttrium analogue of complex 4 yielded single-crystalline material of the tetrahydrofuran adduct DanipY(THF)[O(2,6-diisopropylphenyl)](2) (5). The molecular structures of the complexes 1-4 feature five-coordinate metal atoms and coordination polyhedra which can be described as distorted square-pyramidal rather than trigonal-bipyramidal, with the ipso carbon atom occupying the apical position. On the other hand, the molecular structure of the tetrahydrofuran-solvated yttrium Danip arylalkoxide compound 5 features a six-coordinate metal atom in a distorted trigonal-prismatic coordination environment. In all cases the Danip ligand system adopts the chiral (racemic) d,l form.

Journal Article↗

Combined charge and spin density experimental study of the yttrium(III) semiquinonato complex Y(HBPz3)2(DTBSQ) and DFT calculations.

High-resolution X-ray diffraction and polarized neutron diffraction experiments have been performed on the Y-semiquinonate complex, Y(HBPz3)2(DTBSQ), in order to determine the charge and spin densities in the paramagnetic ground state, S = (1/2). The aim of these combined studies is to bring new insights to the antiferromagnetic coupling mechanism between the semiquinonate radical and the rare earth ion in the isomorphous Gd(HBPz3)2(DTBSQ) complex. The experimental charge density at 106 K yields detailed information about the bonding between the Y3+ ion and the semiquinonate ligand; the topological charge of the yttrium atom indicates a transfer of about 1.5 electrons from the radical toward the Y3+ ion in the complex, in agreement with DFT calculations. The electron density deformation map reveals well-resolved oxygen lone pairs with one lobe polarized toward the yttrium atom. The determination of the induced spin density at 1.9 K under an applied magnetic field of 9.5 T permits the visualization of the delocalized magnetic orbital of the radical throughout the entire molecule. The spin is mainly distributed on the oxygen atoms [O1 (0.12(1) mu B), O2(0.11(1) mu B)] and the carbon atoms [C21 (0.24(1) mu B), C22(0.20(1) mu B), C24(0.16(1) mu B), C25(0.12(1) mu B)] of the carbonyl ring. A significant spin delocalization on the yttrium site of 0.08(2) mu B is observed, proving that a direct overlap with the radical magnetic orbital can occur at the rare earth site and lead to antiferromagnetic coupling. The DFT calculations are in good quantitative agreement with the experimental charge density results, but they underestimate the spin delocalization of the oxygen toward the yttrium and the carbon atoms of the carbonyl ring.

Journal Article↗

Three yttrium crotonate complexes with diimines.

The synthesis and crystal structures of three new yttrium crotonate (crot) compounds, associated with three different nitrogenous bases, namely 1,10-phenanthroline (phen), 4-methyl-1,10-phenanthroline (mphen) and 2,2'-bipyridylamine (bpa), are presented. All three compounds organize as centrosymmetric dimers, to give tetra-micro-crotonato-bis[crotonato(1,10-phenanthroline)yttrium(III)] dihydrate, [Y(2)(C(4)H(5)O(2))(6)(C(12)H(8)N(2))(2)].2H(2)O or [Y(crot)(3)(phen)](2).2H(2)O, (I), tetra-micro-crotonato-bis[crotonato(4-methyl-1,10-phenanthroline)yttrium(III)] dihydrate, [Y(2)(C(4)H(5)O(2))(6)(C(13)H(10)N(2))(2)].2H(2)O or [Y(crot)(3)(mphen)](2).2H(2)O, (II), and tetra-micro-crotonato-bis[diaqua(crotonato)yttrium(III)] 2,2'-bipyridylamine tetrasolvate, [Y(2)(C(4)H(5)O(2))(6)(H(2)O)(4)].4C(10)H(9)N(3) or [Y(crot)(3)(aq)(2)](2).4(bpa), (III). Complexes (I) and (II) are isomorphous, with the bases acting as chelating ligands. In complex (III), the coordination sphere is built up of carboxylate and aqua ligands, with the non-coordinated diimine acting as included solvent.

Journal Article↗

Holmium: yttrium aluminum garnet laser-assisted endoscopic sinus surgery: laboratory experience.

Endoscopic sinus surgery has gained wide acceptance since its introduction into the United States. Complex sinus anatomy and troublesome bleeding have been associated with complications, which vary in severity from synechia to blindness and leakage of cerebrospinal fluid. Endoscopic sinus surgery using a holmium: yttrium aluminum garnet pulsed solid-state laser oscillating at 2.1 microns with fiberoptic delivery was performed in the laboratory, and the results were compared with those of conventional endoscopic sinus surgery. Three beagle dogs, six human cadaver heads, and one calf head were used in the in vivo and in vitro studies to evaluate the bone ablation, tissue coagulation, and hemostatic properties of the holmium: yttrium aluminum garnet laser. Modified endoscopic telescopes for sinus surgery, a newly developed handpiece for fiberoptic delivery, and other surgical instruments were used. The results indicate that the holmium: yttrium aluminum garnet laser and new delivery instrumentation provide good hemostasis and controlled soft-tissue ablation and bone removal. The access to all sinuses in the human cadaver model was very good. The canine in vivo study showed delayed but complete healing on the laser-treated side. Clinical evaluation of the holmium: yttrium aluminum garnet laser is warranted to increase the precision and safety of endoscopic sinus surgery.

Animals↗

Measurements of the refractive index of yttrium in the 50-1300-eV energy region.

The first experimental results to our knowledge on the refractive index n = 1 - delta + ibeta of yttrium in the extreme-ultraviolet and soft x-ray energy ranges are discussed. To determine the absorptive part beta, transmittance measurements were performed on pure yttrium films in the 50-1300-eV energy region at beamline 6.3.2 of the Advanced Light Source. The dispersive part delta was then calculated from the absorption results by means of the Kramers-Kronig transformation. Compared with prior tabulated values, the new wet of data for the refractive index of yttrium is in better agreement with the sum rules and contains previously unresolved fine structure information in the regions of the M2,3 and M4,5 absorption edges, where yttrium-based multilayer mirrors operate.

Journal Article↗