Structural characteristics of the mediodorsal nucleus of the cat thalamus

By means of the light and electron microscopy, construction and architectonics of neurons in the cat thalamus medio-dorsal nucleus are described. Differences in the neuronal body dimentions, their form, number of deferent dendrites and character of axonal branching made it possible to define 3 types of neurons. Applying the method based on retrograde axonal transport of exogenous horse-radish peroxidase, it was demonstrated that neurons of type II, contrary to the existing opinion, send their axons into the prefrontal cortex and, hence, are associative-projective. Ultrastructural difference of axonal terminals, differences in the form and size of synaptic vesicles made it possible to reveal 5 types of presynapses.     

Metacognitive awareness and prevention of relapse in depression: Empirical evidence.

Metacognitive awareness is a cognitive set in which negative thoughts/feelings are experienced as mental events, rather than as the self. The authors hypothesized that (1) reduced metacognitive awareness would be associated with vulnerability to depression and (2) cognitive therapy (CT) and mindfulness-based CT (MBCT) would reduce depressive relapse by increasing metacognitive awareness. They found (1) accessibility of metacognitive sets to depressive cues was less in a vulnerable group (residually depressed patients) than in nondepressed controls; (2) accessibility of metacognitive sets predicted relapse in residually depressed patients; (3) where CT reduced relapse in residually depressed patients, it increased accessibility of metacognitive sets; and (4) where MBCT reduced relapse in recovered depressed patients, it increased accessibility of metacognitive sets. CT and MBCT may reduce relapse by changing relationships to negative thoughts rather than by changing belief in thought content. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The choice of prodrugs for gene directed enzyme prodrug therapy of cancer

Prodrugs are chemicals that are pharmacodynamically and toxicologically inert but which can be converted to highly active species. In cancer chemotherapy, enzyme activated prodrugs have been effective against certain animal tumours. However, in the clinic it has been found that human tumours containing appropriately high levels of the activating enzymes were rare and not associated with any particular type of tumour. Gene directed enzyme prodrug therapy (GDEPT) attempts to overcome this problem by killing tumour cells by the activation of a prodrug after the gene encoding for an activating enzyme has been targeted to the malignant cell. Here we summarise the various enzyme/prodrug systems that have been proposed for cancer therapy and comment on their suitability for GDEPT. This is because systems developed for other applications such as antibody directed enzyme prodrug therapy (ADEPT) may not be suitable for GDEPT. What is required are nontoxic prodrugs that can be converted intracellularly to highly cytotoxic metabolites that are not cell cycle specific in their mechanism of action. The active drugs released should also be readily diffusible and exert a bystander effect. Alkylating agents best meet these criteria. An example of a suitable enzyme/prodrug system may be a bacterial nitroreductase that can convert a relatively nontoxic monofunctional alkylating agent to a difunctional alkylating agent that is some ten thousand times more cytotoxic.     

The effect of hemoglobin and its metabolites on energy metabolism in cultured cerebrovascular smooth-muscle cells

Cerebral arteries in spasm have been found to contain low levels of adenosine triphosphate (ATP), and it has been postulated that this change in levels results from hypoxia produced by arterial encasement in clotted material. This study was undertaken to determine whether any of four blood-derived agents, ferrous hemoglobin, methemoglobin, hemin, or bilirubin, is capable of reducing energy levels in cerebral artery smooth-muscle cells. Twenty-four-hour exposure of cultured canine basilar artery cells to ferrous hemoglobin and bilirubin led to a significant decline in ATP levels (to 8.9 nmol/mg protein and 2.8 nmol/mg protein, respectively) versus control (16.6 nmol/mg protein); methemoglobin and hemin showed no effect. Bilirubin but not hemoglobin was found to interfere with electron transport and with creatine phosphokinase activity in intact cells; however, bilirubin showed no inhibitory effect on this enzyme in cell-free conditions. The findings indicate that hemoglobin and bilirubin may be responsible for diminished energy levels in cerebral arteries. These observations also suggest that bilirubin may exert its effect on ATP by impairing mitochondrial function.     

Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle

It has been suggested, on the basis of immunolocalization studies in vivo and antibody blocking experiments in vitro, that alpha 4 integrins interacting with vascular cell adhesion molecule 1 (VCAM-1) are involved in myogenesis and skeletal muscle development. To test this proposal, we generated embryonic stem (ES) cells homozygous null for the gene encoding the alpha 4 subunit and used them to generate chimeric mice. These chimeric mice showed high contributions of alpha 4-null cells in many tissues, including skeletal muscle, and muscles lacking any detectable (< 2%) alpha 4-positive cells did not reveal any gross morphological abnormalities. Furthermore, assays for in vitro myogenesis using either pure cultures of alpha 4-null myoblasts derived from the chimeras or alpha 4-null ES cells showed conclusively that alpha 4 integrins are not essential for muscle cell fusion and differentiation. Taking these results together, we conclude that alpha 4 integrins appear not to play essential roles in normal skeletal muscle development.