Development of a complementary PET/MR dual-modal imaging probe for targeting prostate-specific membrane antigen (PSMA).

We tried to develop a dual-modal PET/MR imaging probe using a straightforward one-pot method by encapsulation with specific amphiphiles. In this study, iron oxide (IO) nanoparticles were encapsulated with three amphiphiles containing PEG, DOTA and the prostate-specific membrane antigen (PSMA)-targeting ligand in aqueous medium. The diameter of the prepared nanoparticle DOTA-IO-GUL was 11.01±1.54nm. DOTA-IO-GUL was labeled with (68)Ga in high efficiency. The DOTA-IO-GUL showed a dose-dependent binding to LNCaP (PSMA positive) cells via a competitive binding study against (125)I-labeled MIP-1072 (PSMA-targeting agent). Additionally, PET and MR imaging results showed PSMA selective uptake by only 22Rv1 (PSMA positive) but not PC-3 (PSMA negative) in dual-tumor xenograft mouse model study. MR imaging showed high resolution, and PET imaging enabled quantification and confirmation of the specificity. In conclusion, we have successfully developed the specific PSMA-targeting IO nanoparticle, DOTA-IO-GUL, as a dual-modality probe for complementary PET/MR imaging. FROM THE CLINICAL EDITOR: The combination of using Positron Emission Tomography (PET) and computed tomography (CT) in clinical practice is now the norm. With advances in technology, the next step would be to develop combined PET and Magnetic Resonance (MR) dual-imaging. In this article, the authors described their positive study on the development of a dual-modal PET/MR imaging probe using a prostate cancer model.

Identification of mouse langerin/CD207 in Langerhans cells and some dendritic cells of lymphoid tissues.

Human (h)Langerin/CD207 is a C-type lectin of Langerhans cells (LC) that induces the formation of Birbeck granules (BG). In this study, we have cloned a cDNA-encoding mouse (m)Langerin. The predicted protein is 66% homologous to hLangerin with conservation of its particular features. The organization of human and mouse Langerin genes are similar, consisting of six exons, three of which encode the carbohydrate recognition domain. The mLangerin gene maps to chromosome 6D, syntenic to the human gene on chromosome 2p13. mLangerin protein, detected by a mAb as a 48-kDa species, is abundant in epidermal LC in situ and is down-regulated upon culture. A subset of cells also expresses mLangerin in bone marrow cultures supplemented with TGF-beta. Notably, dendritic cells in thymic medulla are mLangerin-positive. By contrast, only scattered cells express mLangerin in lymph nodes and spleen. mLangerin mRNA is also detected in some nonlymphoid tissues (e.g., lung, liver, and heart). Similarly to hLangerin, a network of BG form upon transfection of mLangerin cDNA into fibroblasts. Interestingly, substitution of a conserved residue (Phe(244) to Leu) within the carbohydrate recognition domain transforms the BG in transfectant cells into structures resembling cored tubules, previously described in mouse LC. Our findings should facilitate further characterization of mouse LC, and provide insight into a plasticity of dendritic cell organelles which may have important functional consequences.

[The isolation of the surface antigen from vegetative cells of Bacillus anthracis STI-1 and study of its protective properties]. / Vydelenie poverkhnostnogo antigena vegetativnykh kletok Bacillus anthracis STI-1 i izuchnie ego protektivnykh svoistv.

The method for the extraction of native surface protein antigen with a mol. wt. of 92 kD from vegetative cells of B.anthracis STI-1 and its purification was developed. The antigen was extracted with 3% sodium lauryl sarcosylate at 4 degrees C from bacterial mass previously treated with 0.1 M tris-HCl buffer solution, pH 8.0 Purification was carried out by adsorption chromatography on hydroxylapatite. The isolated protein antigen with a mol. wt. of 92 kD was electrophoretically and immunochemically homogeneous. The study of the protective properties of this protein in combination with Freund's adjuvant, made on white mice, revealed that it had good prospects for use in the creation of chemical vaccines against the causative agent of anthrax.

Inactivación in vitro del Ags HB por extractos de plantas del género Phyllantus / In vitro inactivation of Ags HB by plant extracts of the Phyllanthus genus

Se estudiaron 3 especies del género Phyllanthus procedentes de la zona oriental de Cuba con el fin de determinar la capacidad inanctivante del antígeno de superficie (Ags HB) del virus hepatitis B in vitro. Para ello se prepararon extractos alcohólicos de cada especie y de diferentes partes de dichas plantas, con las cuales se trataron sueros de pacientes positivos al Ags HB. Los resultaron demuestran que las especies estudiadas poseen la propiedad de inactivar dicho antígeno entre el 93 y el 97 por ciento de los sueros ensayados. El análisis de la capacidad de inactivación de las 3 partes del Phyllanthus chamaecristoides reveló una mayor actividad en los extractos de tallos (97 por ciento), con un comportamiento similar en las 2 temperaturas de incubación utilizadas. Se observa presencia de flavonoides en el extracto de esta especie (AU)

Lymphocyte profiles in patients with chronic low back pain enrolled in a clinical trial.

OBJECTIVE: Our earlier findings suggest that patients with musculoskeletal complaints have lower numbers and percentages of natural killer (NK) cells than asymptomatic subjects. This study examines patient lymphocyte profiles, as a secondary outcome measure, in a trial of manipulative therapies to treat chronic low back pain (LBP) of mechanical origin. DESIGN: The patients were compared in a randomized controlled trial. Baseline measures were collected at the initial visit; all patients were scheduled for 11 treatments in 14 days. Treatment consisted of either a high-force, high-velocity, low-amplitude manipulation procedure; a low-force, high-velocity, low-amplitude procedure or a series of educational lectures on lower back pain. Posttreatment measures were collected at the final treatment session; follow-up measures were obtained 2 wk later. SETTING: The study was conducted at a chiropractic teaching clinic in the suburban Chicago area. PARTICIPANTS: Individuals over 18 were eligible if they were new patients or repeat patients with a 6 month's hiatus, if the chief complaint was LBP of greater than 50 days' duration, if pain was elicited with palpation over one or more of the facet joints from the spinal levels between L1 and S1 and including the sacroiliac joints, and if there was absence of pain referral or if pain referral was only scleratogenous in nature. Criteria for excluding patients included hard neurologic signs, systemic disease potentially affecting the musculoskeletal system, contraindication to spinal manipulation such as osteoporosis, fracture or other bony pathology, or treatment with medication intended to relieve symptoms associated with their LBP. Eligibility was determined by a staff diagnostic team independent of the attending physician. Three hundred sixty-seven of 1,275 consecutive new patients met the eligibility criteria. Of these, 209 participated. These results are for 201 patients from whom flow cytometric data were obtained. OUTCOME MEASURES: Both absolute numbers and percentages of B-lymphocytes, T-lymphocytes, T-Helper (TH), T-Suppressor (TS) and NK lymphocytes were determined. Blood samples were collected at the same time that the primary outcome measures were obtained. Cells were stained with two-color monoclonal antibodies directed against specific cell surface antigens, and each lymphocyte subpopulation was quantified directly from lysed whole blood with a Coulter Epics Profile II flow cytometer. RESULTS: Thirty-five patients dropped out before the follow-up visit and technical problems resulted in the loss of data from 17 more and the exclusion of some subpopulation data. In all, 148 cases were analyzed for B cells, 146 for TH, TS and NK cells and 138 for cells that carried both the NK and TS marker. A one-way analysis of variance revealed no significant differences in the lymphocyte profiles at baseline among the three groups. All subpopulation baseline values were within reported reference ranges for normal adult populations. However, the percentage of NK cells (9.1%) was below the published minimum critical value. A repeated measures analysis of variance was used to determine whether treatment effects changed over time, that is, treatment-time interaction. The cell types for which the interaction tests were at or near statistical significance were: TH cells (p = .0208), total T cell percent (p = .0928) and absolute total T cells (p = .0908). Interaction tests for differences in either percent or absolute counts of B cells, TS cells, or NK cells were not statistically significant. CONCLUSIONS: This is the first report of lymphocyte profiles in patients with diagnosed chronic LBP. Our finding of a lower percentage of NK cells in these patients confirms our earlier finding that patients with musculoskeletal problems have a lower percentage of NK cells than do asymptomatic subjects. However, manipulative therapy was not shown to have a clinically significant effect on either the absolute n

Septicemia caused by cysteine-dependent Escherichia coli.

A case of septicemia and urinary tract infection caused by cysteine-dependent Escherichia coli in a 70-year-old woman with bilateral staghorn calculi is described. This is the second report of a cysteine-dependent E. coli bacteremia. The bacterium was falsely susceptible to ampicillin and co-trimoxazole when tested on a medium without cysteine supplement.

[The potentials for immunization against influenza using liposome-incorporated viral surface antigens]. / Possibilités d'immunisation contre la grippe à l'aide d'antigènes viraux de surface incorporés aux liposomes.

Studies were conducted using uni- and multilamellar liposomes to establish optimum conditions for influenza antigen incorporation in view of their transport to the target cells for experimental influenza prophylaxis in hybrid white mice. Radiometric determinations showed a good level of preparation purification, a good efficiency of incorporation in liposomes of the active biological material, the liposome linked radioactivity distribution among different organs. Charged liposomes induced solid and long lasting resistance against influenza control infection.

A glycophospholipid tail at the carboxyl terminus of the Thy-1 glycoprotein of neurons and thymocytes.

Cell surface molecules of eukaryotic cells have been considered to be integrated into the membrane bilayer by a transmembrane protein sequence. The Thy-1 antigen of rodent thymocytes and brain was the first eukaryotic membrane molecule for which biochemical data clearly suggested membrane integration via a nonprotein tail. Direct evidence is now presented showing that a glycophospholipid structure is attached to the carboxyl-terminal cysteine residue and that 31 carboxyl-terminal amino acids predicted from the Thy-1 complementary DNA sequence are not present in the mature glycoprotein. These experimental results raise questions concerning signaling across a cell membrane since antibodies to Thy-1 can stimulate T lymphocytes to release lymphokines and undergo cell division.

Initial characterization of Trypanosoma lewisi surface membrane antigen.

The purified T. lewisi were subjected to hypotonic lysis plus freezing and thawing in acetone dry ice bath. The trypanosome ghosts were obtained after repeated washing and centrifugation. The homogenized ghost suspension was assayed for enzyme Na++K+ ATPase activity to ratify the presence of the trypanosome surface membrane. Membrane solubilized in sodium dodecyl sulfate were fractionated by gel filtration on Sephadex columns equilibrated with the detergent and electrophoresis in polyacrylamide gel. Crude trypanosome surface membrane antigens were tested for their immunogenicity, administered to rats in Fraund's complete adjuvant. The results of these experiments indicated that the protective immunogen is tightly bound to the membrane since the use of strong anionic detergent is necessary in its extraction.