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L Josephson

Publications and source records attributed to L Josephson.

At least 19 recordsLinked to original sources
PubMed2001

Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles.

The present study analyzed the feasibility of using magnetic resonance imaging (MRI) to monitor T-cell homing in vivo after loading T cells with superparamagnetic iron oxide (CLIO) nanoparticles derivatized with a peptide sequence from the transactivator protein (Tat) of HIV-1. T cells were isolated from C57BL/6 (B6) mice and loaded with 0, 400, 800, 1600, or 8000 ng/ml of FITC conjugated CLIO-Tat (FITC-CLIO-Tat). There was a dose-dependent uptake of FITC-CLIO-Tat by T cells. Stimulation of FITC-CLIO-Tat loaded T cells with anti-CD3 (0.1 microg/ml) plus IL-2 (5 ng/ml) elicited normal activation and activation-induced cell death (AICD) responses, and normal upregulation of CD69, ICAM-1 (CD54), L-selectin (CD62L), and Fas. The FITC-CLIO-Tat loaded T cells (3 x 10(7)) were transferred intravenously (i.v.) into B6 mice and the in vivo MRI of mice was acquired using a spin-echo pulse sequence at 4.7 T with a Bruker Biospec system. Homing of T cells into the spleen was observed by a decrease in MRI signal intensity within 1 h after the transfer, which remained decreased for 2-24 h after transfer. These homing data were confirmed by FACS analysis and biodistribution analysis using 125I-CLIO-Tat. Thus, T cells can be efficiently loaded with FITC-CLIO-Tat without interfering with their normal activation and AICD, or homing to the spleen, and the biodistribution of FITC-CLIO-Tat loaded T cells can be monitored in vivo over time by MRI.

Animals↗
PubMed2001

Human transferrin receptor gene as a marker gene for MR imaging.

PURPOSE: To quantitate and characterize the expression of an engineered human transferrin receptor (ETR) as a marker gene by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: Rat gliosarcoma 9L cells stably expressing ETR (ETR+) were used, with nontransfected (ETR-) cells serving as controls. A conjugate of transferrin and monocrystalline iron oxide (Tf-MION) nanoparticles was synthesized to probe for the activity of ETR. Accumulation of Tf-MION was examined by using cell internalization in culture and MR (n = 6) and nuclear (n = 4) imaging in a mouse model with ETR+ and ETR- tumors implanted in the opposite flanks. Autoradiographic and histopathologic results were correlated with MR findings. RESULTS: Tf-MION was internalized by ETR+ cells at 37 degrees C but not at 4 degrees C. Rhodamine-labeled Tf-MION and fluorescein-labeled antibody to ETR colocalized in small vesicle-like structures in the cytoplasm. Both findings were consistent with accumulation by the receptor-mediated endocytosis mechanism of ETR. Compared with ETR- tumors, ETR+ tumors accumulated more Tf-MION and had higher signal intensity on T1-weighted MR images and lower signal intensity on T2-weighted images. Autoradiographic findings showed a spatial correlation between MR signal intensity and TF-MION accumulation. CONCLUSION: ETR+ tumors internalize the MR imaging probe through the action of transferrin receptor in amounts that can be detected with MR imaging.

Animals↗
PubMed1996

Antiviral activity of a conjugate of adenine-9-beta-D-arabinofuranoside 5'-monophosphate and a 9 kDa fragment of arabinogalactan.

An arabinogalactan conjugate containing a 9 kDa fragment of arabinogalactan and adenine-9-beta-D-arabinofuranoside 5'-monophosphate (araAMP), denoted AG(9 kDa)-araAMP, has been synthesized and characterized. In 2.2.15 (human hepatoblastoma) cells, the attachment of araAMP to AG(9 kDa), a ligand of the asialoglycoprotein receptor, decreased the effective concentration for inhibiting extracellular hepatitis B virus (HBV) production by 90% (EC90) from 17 to 0.9 microM adenine arabinoside (araA) equivalents, and increased the cytotoxic concentration (CC50) from 188 to > 17 300 microM araA equivalents. Hence, the selectivity index (CC50/EC90) of araA was improved from 11 (188/17) to > 19200 (17 300/0.9) by conjugation with the 9 kDa fragment of arabinogalactan. AG(9 kDa)-araAMP did not affect the production of viral RNA or viral proteins. In the woodchuck hepatitis model, AG(9 kDa)-araAMP inhibited woodchuck hepatitis virus (WHV) DNA replication at a dose of 0.3 mg of araA equivalents per kg; in this case, AG(9 kDa)-araAMP was 20-30 times more potent than was unconjugated araA. AG(9 kDa)-araAMP was effective by intramuscular or subcutaneous administration. The reduction in HBV DNA levels obtained in 2.2.15 cells and of WHV DNA levels in woodchucks was sustained after treatment with AG(9 kDa)-araAMP ceased. In both cases, viral DNA gradually returned to pre-treatment levels.

Animals↗
PubMed1994

Visualization of superior mesenteric lymph nodes by the combined oral and intravenous administration of the ultrasmall superparamagnetic iron oxide, AMI-227.

Superior mesentric lymph nodes which lie as a chain near the small intestine are difficult to visualize in the rat with MRI either with or without the use of contrast agents. We previously demonstrated that the oral administration of an ultrasmall superparamagnetic iron oxide (AMI-227) produces a brightening of the lumen of the GI tract with a T1-weighted spin-echo pulse sequence. We have also shown that AMI-227 darkens abdominal lymph nodes. In the present study we show that the combined oral and intravenous administration of AMI-227 produces a brightening of the lumen of the GI tract and a darkening of the superior mesenteric lymph node chain. As a result of these combined and opposing effects on image signal intensity, a necessary contrast is established to reliably locate the superior mesenteric lymph nodes in vivo, which, to our knowledge, have been elusive by other techniques.

Administration, Oral↗
PubMed1994

Use of AMI-227 as an oral MR contrast agent.

We report the use of an ultrasmall superparamagnetic iron oxide colloid AMI-227 as an oral contrast agent. Due to the small size, AMI-227 has a larger effect on T1 than larger superparamagnetic iron oxides colloids like ferumoxsil. At 2 T, AMI-227 had an R2/R1 of 11.4 compared with an R2/R1 for the superparamagnetic iron oxide ferumoxsil of 179. The R1s of the two agents were 7.1 and 1.6 mM-1 s-1, for AMI-227 and ferumoxsil, respectively. Due to its smaller R2/R1, orally administered AMI-227 can produce brightening or darkening of the lumen of the GI tract, depending on instrument parameters. At 1 mM Fe, image brightening (2 T, TR = 300, TE = 25) or image darkening of the GI tract (2 T, TR = 1500, TE = 80) was obtained. The ability of AMI-227 to produce either image brightening or darkening suggests it may be useful as an MR contrast agent for the GI tract.

Abdomen↗
PubMed1994

Biodistribution of an ultrasmall superparamagnetic iron oxide colloid, BMS 180549, by different routes of administration.

The ultrasmall superparamagnetic iron oxide colloid BMS 180549 can be found lymph nodes by either subcutaneous (SC) or intravenous (IV) injection. With an SC injection in the front extremities, the axillary and brachial nodes attain the highest accumulations of the agent. With an SC injection in the rear extremities, the popliteal, iliac, and axillary nodes attain highest accumulations of the agent. With IV injection of the agent, the iliac, mediastinal and mesenteric nodes attain highest accumulations of the agent. Though the spleen is not involved with the drainage of the interstitial space near the site of SC injections, the mobility of BMS 180549 from such injection sites increases splenic relaxation rates. Based on a knowledge of the lymphatic system, a route of administration of BMS 180549 can be chosen to maximize the delivery of the agent to specific lymph nodes.

Animals↗
PubMed1991

The magnetic properties of some materials affecting MR images.

We have compared the magnetic properties of various types of materials known to affect MR images. The materials compared were: (i) MR contrast agents based on chelates of paramagnetic metals (Gd-DTPA, Dy-DTPA); (ii) biological forms of iron (horse spleen ferritin and deoxyhemoglobin); and (iii) a superparamagnetic iron oxide (AMI-25). The properties compared were the magnetic susceptibility and the magnetization. The magnetization and susceptibility of superparamagnetic AMI-25 are far larger than that of ferritin or low molecular weight, paramagnetic chelates. Superparamagnetic iron oxide colloids, like AMI-25, are a uniquely powerful class of magnetic materials.

Animals↗
PubMed1990

A functionalized superparamagnetic iron oxide colloid as a receptor directed MR contrast agent.

We have synthesized a surface functionalized superparamagnetic iron oxide colloid whose clearance from the vascular compartment was inhibited by asialofetuin but not fetuin. Unlike other particulate or colloidal magnetic resonance (MR) contrast agents, the agent of the current communication is not withdrawn from the vascular compartment by cells of the macrophage-monocyte phagocytic system, as indicated by its selective increase in hepatic relaxation rates. Because of this we refer to this colloid as a hepatic selective (HS) MR contrast agent. At 20 mumol Fe/kg the HS MR agent darkened MR images of liver. The HS MR agent exhibited no acute toxicity when injected into rats at 1800 mumol Fe/kg. Based on these observations, surface functionalized superparamagnetic iron oxide colloids may be the basis of MR contrast agents internalized by receptor mediated endocytosis generally, and by the asialoglycoprotein receptor in particular.

Animals↗
PubMed1990

Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging.

An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm. The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular transport and through interendothelial junctions. Twenty-four hours after intravenous administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (d) the magnetic moiety in organ-targeted superparamagnetic contrast agents for magnetic resonance imaging.

Animals↗
PubMed1990

Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging.

An ultrasmall superparamagnetic iron oxide (USPIO) preparation was evaluated as a potential intravenous contrast agent for lymph nodes. Relaxation time measurements and magnetic resonance (MR) imaging were performed in rats with normal lymph nodes and in rats with lymph node metastases. In normal animals, lymph node relaxation times decreased maximally within 24-48 hours after intravenous administration of USPIO. Twenty-four hours after administration, the T2 of normal lymph nodes had decreased from 74 msec +/- 2.2 to 30 msec +/- 0.7 (USPIO, 40 mumol of iron per kilogram) or 15 msec +/- 0.0 (200 mumol Fe/kg), whereas the T2 of metastatic nodes did not change. MR imaging of the animal model of nodal metastases confirmed the hypothesis that intravenously administered USPIO decreases signal intensity of normal but not metastatic nodes. A single intravenous administration of USPIO may allow detection of nodal metastases on the basis of signal intensity characteristics rather than the currently used, insensitive size characteristics.

Animals↗
PubMed1989

Experimental lymph node metastases: enhanced detection with MR lymphography.

Magnetic resonance (MR) lymphography with superparamagnetic iron oxide (AMI-25) as a contrast agent was developed in an animal model with tumor-bearing lymph nodes. After interstitial administration of 20 mumol of iron per kilogram of body weight into the footpads of rats, the T2 of popliteal and paraaortic lymph nodes decreased from 67 msec +/- 8.2 to 9.5 msec +/- 0.9 and 9.3 msec +/- 0.9, respectively. T2 relaxation times of lymph nodes containing metastases showed a significantly higher value (61 msec +/- 6.2, P less than .005) after interstitial administration of the contrast agent. Intravenous administration of AMI-25 did not produce enhancement of normal or metastatic lymph node relaxation times. The signal intensity of normal lymph nodes decreased profoundly on spin-echo MR images (repetition time of 500 msec, echo time of 30 msec) after interstitial administration, whereas lymph nodes with metastases showed no significant change in signal intensity. Experimental results indicate that MR lymphography may potentially increase the sensitivity of MR imaging the detection of lymphatic malignancy.

Animals↗
PubMed1979

Stability of dilute solutions of gentamicin and tobramycin.

Dilution of sera containing gentamicin or tobramycin in glass containers results in substantial adsorption of the antibiotic to the surface of the container, which can be prevented if acidic or basic solutions are used to dilute such sera. We describe protocols for radioimmunoassays of gentamicin and tobramycin that include solutions and containers that obviate this problem.

Adsorption↗