Prodrugs for targeting hypoxic tissues: regiospecific elimination of aspirin from reduced indolequinones

We report the cases of three patients with anorexia nervosa (AN) who each recovered rapidly after experiencing a life-threatening episode with severe thrombocytopenia. All three cases were the typical restricting-type of AN, occurring in adolescence. They refused to be admitted to a hospital until their general condition had been severely deteriorated. Their lowest platelet counts were 2.9, 4.6, and 2.3 x 10(4)/mm3, respectively. Apparent hemorrhagic tendencies, such as purpura, gingival and nasal bleeding, and gastrointestinal bleeding were observed. The bone marrow examination showed apparent hypoplasia in two patients. No evidence of disseminated intravascular coagulation or autoantibody to platelets was detected. The platelet counts recovered rapidly by water and nutritional supplementation. The recovery from the AN itself was excellent in all three patients without specific psychotherapy.     

Kalirin inhibition of inducible nitric-oxide synthase

Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity.     

Automated detection of bolus arrival and initiation of data acquisition in fast, three-dimensional, gadolinium-enhanced MR angiography

Automatic triggering of magnetic resonance (MR) angiography with detection of a contrast material bolus was evaluated. Signal intensity changes with time were tracked in a prescribed tracking or monitoring volume by a parallel signal processing unit that automatically started data acquisition once user-defined thresholds were exceeded. This technique, referred to as MR Smartprep, was reliable and avoided the inconsistencies of manual timing.     

Quantal currents and potential in the three-dimensional anisotropic bidomain model of smooth muscle

The potential generated in the smooth muscle of the vas deferens on release of a quantum of transmitter from a varicosity was analyzed using a three-dimensional bidomain continuum model. Current was injected at the origin of the bidomain; this current had the temporal characteristics of the junctional current. The membrane potential, intracellular potential, and extracellular potential, as well as the extracellular current, were then calculated throughout the bidomain at different times. Calculations were performed to show the effect of changing the anisotropy ratios of the intracellular and extracellular conductivities on the spread of current and potential in each of the three dimensions. These results provide a theoretical framework for ascertaining the time course of transmitter interaction at a varicosity following the secretion of a quantum of transmitter.     

Improved targeting of an anti-epidermal growth factor receptor variant III monoclonal antibody in tumor xenografts after labeling using N-succinimidyl 5-iodo-3-pyridinecarboxylate

The crystal structure is reported of a complex between the dodecanucleotide sequence d(CGCGAATTCGCG)2and an analogue of the DNA binding drug Hoechst 33258, in which the piperazine ring has been replaced by an amidinium group and the phenol ring by a phenylamidinium group. The structure has been refined to an R factor of 19.5% at 2.2 A resolution. The drug is held in the minor groove by five strong hydrogen bonds, together with bridging water molecules at both ends. There are few other contacts with the floor of the groove, indicating a lack of isohelicity with the groove and suggesting (i) that the observed high DNA affinity of this drug is primarily due to the array of hydrogen bonds and (ii) that these more than compensate for its poor isohelicity.     

Fast fluid-attenuated inversion-recovery imaging: first experience with a 3D version in epilepsy

Breast reconstruction has been the subject of many controversies. It now seems generally agreed however that the operation has no deleterious influence on the follow up of breast cancer patients and that it has favorable psychologic effects. Breast reconstruction can be performed either by using prostheses or analogous tissues. These two different modalities have each their own advantages and limitations. Deep knowledge of the techniques and their indications allows to select the most appropriate approach in the individual patient and, thus, to improve long term results.     

Memory for emotional trait adjectives in clinically depressed youth

An experiment was conducted to examine memory for emotional trait adjectives in depressed children and adolescents. Two groups of children and adolescents, clinically depressed participants and non-clinical controls, were compared on computerized versions of recall and recognition memory tasks. Three groups of words (positive trait adjectives, negative trait adjectives, and categorized neutral words) were used in the experiment. Results showed that the depressed group recalled significantly more negative adjectives than positive adjectives, whereas the control group recalled the same number of positive and negative adjectives. This effect was predicted by the association between age and level of depression, with the depression-related bias becoming stronger with age. Signal detection analysis revealed that the depressed group did not show any bias in the recognition task. The findings are discussed with respect to cognitive theories of depression with consideration of the developmental implications.