Cytogenetic effects of methylmercury in embryos of the killifish,Fundulus heteroclitus

Fertilized eggs of the killifish,Fundulus heteroclitus, were exposed experimentally to methylmercury (MeHg) to evaluate whether this compound induced cytogenetic effects expressed in the embryos. An additional objective was to assess cytogenetically whetherFundulus embryos from groups that were determined to be more susceptible to the teratogenic effects of MeHg were also more susceptible to its mutagenic effects. Embryos exposed to 0.05 mg/L MeHg for 1 and 7 days post-fertilization were preserved in 10% formalin for cytological examination, while unfixed embryos from the same clutches were evaluated for teratogenic effects. Untreated embyros from each clutch served as controls. Cytogenetic-cytological analyses of fixed treated susceptible embryos that exhibited teratogenic effects revealed decreased mitotic counts (5.0-fold), and increased chromosomal aberrations (2.5-fold) when compared to their controls. There were also decreased mitotic counts (1.5-fold) and increased chromosomal aberrations (2-fold) in embryos from resistant groups when compared to their controls. Exposure to MeHg also retarded development. Forty to fifty percent of the susceptible and resistant control embryos reached the tail-bud stage, but only 28% of the treated resistant and none of the treated susceptible embryos reached this stage. There was also a significant correlation (P < 0.05) between teratogenic and mutagenic effects of MeHg in early stages ofFundulus.     

Assessing psychodynamic conflicts: I. Reliability of the idiographic conflict formulation method

Recent years have seen increasing interest in devising methods of studying psychodynamic phenomena. These efforts have had confront difficulties, first, in specifying the data, the observation language, and rules of inference for psychodynamic propositions, and second, in determining the reliability and validity of the measures used. Given how "fuzzy" traditional psychodynamic concepts are, it is no wonder that psychodynamic clinicians from Freud onward have achieved more success in generating new hypotheses than in testing their validity. As Reichenbach (1938) has observed, science requires that discovery be followed by systematic validation of all new propositions, regardless of their degree of popular acceptance. At the core of efforts to study psychodynamics have been methods to study ego functioning (Bellak and Goldsmith 1984), defense mechanisms (Perry and Copper 1988), and psychodynamic conflicts. This paper reports on the reliability of the Idiographic Conflict Formulation (ICF), a guided method for formulating an individual's psychodynamic conflicts.     

The projection of the temporal retina in rats,studied by retrograde transport of horseradish peroxidase

Summary Horseradish peroxidase (HRP) was injected unilaterally into the lateral geniculate nucleus or tectum, or both, in 26 hooded rats in order to mark the exact extent of the retina from which uncrossed optic axons arise. This region occupied about a quarter of the retina, in the temporal periphery, following thalamic injections, but a much smaller region following tectal injections. By comparing the proportions of HRP positive neurones in nasal and temporal retinae of both eyes it was shown that: (1) within the region supplying uncrossed axons the majority of the ganglion cells nevertheless project contralaterally, (2) a large proportion of the ganglion cells from the temporal crescent project bilaterally, which does not occur from the remainder of the retina, (3) ganglion cells of all sizes contribute to both ipsilateral and contralateral projections. The results also support earlier suggestions that the smallest neurones in the ganglion cell layer do not send an axon into the brain, and are therefore not ganglion cells     

Changes in the retino-fugal pathways following cortical and tectal lesions in neonatal and adult rats

Summary Several months after unilateral removal of the striate cortex or superior colliculus, or both, in infant and adult rats the retinal projections were studied autoradiographically. The retinal projection areas in adult-operated animals were not different from those of unoperated controls, but aberrant pathways were found in the infant group. Following removal of striate cortex there was a small aberrant pathway to the lateral posterior nucleus of the thalamus (LP) and possibly to the pretectum. After removal of the superior colliculus there was a conspicuous aberrant projection to LP, which was even more prominent after combined removal of striate cortex and superior colliculus. The results support the proposal that when the normal field of termination is damaged, either directly by a tectal lesion or indirectly by a cortical lesion, axons grow and innervate LP, which has been partly deafferented by the lesion and which consequently possesses vacant synaptic space. Although the different consequences of early and late lesions may indicate that only infantile damaged terminals can redistribute themselves an alternative is that in infants many axons have not yet reached their normal terminal sites at the time of operation and that only those axons have the ability to continue growing and to form an aberrant pathways. The role of the aberrant pathway in vision is unknown.     

Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease

Metal-catalyzed hydroxyl radicals are potent mediators of cellular injury, affecting every category of macromolecule, and are central to the oxidative injury hypothesis of Alzheimer disease (AD) pathogenesis. Studies on redox-competent copper and iron indicate that redox activity in AD resides exclusively within the neuronal cytosol and that chelation with deferoxamine, DTPA, or, more recently, iodochlorhydroxyquin, removes this activity. We have also found that while proteins that accumulate in AD possess metal-binding sites, metal-associated cellular redox activity is primarily dependent on metals associated with nucleic acid, specifically cytoplasmic RNA. These findings indicate aberrations in iron homeostasis that, we suspect, arise primarily from heme, since heme oxygenase-1, an enzyme that catalyzes the conversion of heme to iron and biliverdin, is increased in AD, and mitochondria, since mitochondria turnover, mitochondrial DNA, and cytochrome C oxidative activity are all increased in AD. These findings, as well as studies demonstrating a reduction in microtubule density in AD neurons, suggest that mitochondrial dysfunction, acting in concert with cytoskeletal pathology, serves to increase redox-active heavy metals and initiates a cascade of abnormal events culminating in AD pathology.     

Effect of chronic vincristine treatment on mechanical withdrawal response and pre-pulse inhibition in the rat

Chemotherapeutic agents are associated with a number of serious side-effects. In addition to the development of peripheral neuropathy, patients often complain of additional symptoms related to attentional mechanisms. Although a great deal of interest is directed towards understanding the mechanisms underlying the development of peripheral neuropathy, there is a paucity of research that has examined the extent of impairment of attention in animals receiving chemotherapeutic agents. Therefore, the purpose of this experiment was to examine attentional mechanisms using the method of pre-pulse inhibition in animals that were chronically treated with vincristine. Although vincristine treated animals developed signs of peripheral neuropathy, there was no associated alteration of pre-pulse inhibition relative to vehicle treated animals. These results highlight the importance of continuing to develop methodology to model symptom burden in patients receiving chemotherapy.     

Mechanisms for differential block among single myelinated and non-myelinated axons by procaine

1. The differential sensitivity of saphenous nerve fibres in the cat to block by procaine HCl was re-examined by recording identifiable unit action potentials from small nerve filaments.2. Small myelinated axons were blocked more quickly than large myelinated axons, but this differential effect could not be accounted for by differences in anaesthetic concentration requirements.3. The onset of block in non-myelinated axons was slower than or equal to that of small myelinated axons depending on anaesthetic concentration.4. Absolute differential block of non-myelinated and small myelinated axons was obtained by limiting the length of axons exposed to procaine to 2 mm.5. Differential rates of blocking among myelinated axons appear to depend on differences in the length of axons that must be exposed to blocking concentrations of procaine and to arise from the irregular distribution of such concentrations within an exposed nerve.