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The effect of ligand structure on the magnetic resonance (MR) imaging and biodistribution of six gadolinium (Gd) chelates based on a hydroxypyridonate−terephthalimide (HOPO−TAM) ligand design was investigated. Modifications to the molecular structure of the Gd−HOPO−TAM chelates (hydrophilicity and aromatic group substitution) significantly influence the efficacy of imaging and biodistribution. MR imaging was performed on female mice after intravenous (iv) injection of 100 μmol of Gd/kg of body weight of the different complexes. The biodistribution results indicate that the liver uptake of the complexes is enhanced by a short poly(ethyleneoxy) (PEO) chain, while blood pool localization is facilitated by a very long PEO chain. There is a direct correlation between the blood pool localization of the complexes and the signal intensity of blood vessels in the MRI. The imaging results are consistent with in vitro NMR measurements that indicate long PEO chains increase image enhancement capabilities in the presence of serum albumin.

Proteins of the Hsp70 family of ATPases interact with a conserved domain of their J-protein partners, the J-domain, to function in numerous cellular processes. We have studied the interaction of BiP, an Hsp70 family member in the lumen of the endoplasmic reticulum, with the J-domain of Sec63p, a component of the Sec complex involved in post-translational protein translocation across the endoplasmic reticulum membrane. In a real-time solid phase binding assay, BiP binds to the immobilized Sec complex or to a fusion protein of the J-domain and glutathione S-transferase in a reaction that requires ATP hydrolysis. In the final complex, BiP is bound in the ADP form with its peptide binding pocket occupied. An intact peptide binding pocket is required for this interaction. Our experiments suggest that the activation of BiP by the J-domain involves a transient contact between these components, and that in the absence of physiological substrates, J-activated BiP binds even to the J-proteins themselves.

The detection of metastasis in lymph nodes is greatly enhanced by the use of contrast media. Interstitial injection of lymphography contrast agents requires only injection of a low dose of the agent, and leads to high accumulation in regional lymph nodes with only minor side effects.We were able to show the suitability of liposome-encapsulated gadobutrol as an interstitially injectable lymphography contrast agent in an experimental animal model. For screening of possible lymphotrophic compounds a guinea pig model was used. Accumulation of the contrast agent in 3 successive lymph node groups was determined 4 h after subcutaneous injection of the contrast agent (about 0.1 ml of a 30 mmol Gd/1 solution resulting in a total dose of 10 μmol/kg) into the interdigital skin fold of a hind limb. The Gd concentration in the first lymph node group (popliteal) was 540 μmol/1 (16% dose/g tissue), in the second group (inguinal): 260 μmol/1 (8% dose/g tissue), and in the third group (iliacal): 910 μmol/1 (27% dose/g tissue).Moreover, this compound was completely eliminated and well tolerated.

Symptoms of cerebrovascular events differ depending on the hemisphere in which the lesion arises, thereby affecting disease recognition and management. We aimed to establish whether left and right hemispheric strokes are unequally distributed in inpatients. We obtained data from a large hospital-based stroke registry in Germany. 11@?328 patients (56%) had left hemispheric events and 8769 (44%) had right-sided lesions (p<0.0001). Age, stroke severity, and time from symptom onset to admission were significantly associated with left hemispheric stroke, suggesting a selection effect. Difficulties in recognition of symptoms due to right hemispheric stroke challenge efforts to optimise stroke management, particularly in the critical early hours of stroke.