Cochlear ablation in deafness mutant mice: 2-deoxyglucose analysis suggests no spontaneous activity of cochlear origin

Deafness mutant mice show no stimulus-related cochlear potentials as well as abnormal electrically-evoked responses recorded from the inferior colliculus. Abnormal spontaneous activity in the auditory periphery could result in abnormal development and/or maintenance of the central auditory pathways. We therefore assessed spontaneous activity of cochlear origin in the central nuclei of the mutants by ablating one cochlea and subsequently using the 2-deoxyglucose (2DG) technique to study metabolic activity. Any asymmetries in labeling in a given nucleus should be due to spontaneous activity in the cochlear nerve on the unoperated side. In control animals (+/dn mice undergoing unilateral cochlea ablation), statistically significant decreased 2DG labeling was observed in the ipsilateral PVCN and AVCN, and contralateral MNTB and IC; all receive primary excitatory input from the ablated ear. No significant differences in labeling between right and left sides were observed in any of the nuclei studied in the mutant animals. These findings suggest that there is no spontaneous activity of cochlear origin in these mutants, even though many cochlear nerve fibers and spiral ganglion cells survive.     

Lobucavir-induced proliferative changes in mice

Nucleoside analogues are used in the treatment of viral infections, including those caused by human immunodeficiency virus, cytomegalovirus, and herpes virus. These drugs are beneficial in the treatment of human disease, but are associated with toxicities that often limit their intended therapeutic use, including anemia, neutropenia, peripheral neuropathy, and myopathy. Some of these compounds have been reported to be carcinogenic in rodents. To investigate the carcinogenic potential of lobucavir, a nucleoside analogue, three groups of 60 male and female mice were orally administered lobucavir at daily doses of 10, 50, and 250 mg/kg (males) or 30, 150, and 750 mg/kg (females) over a period of 104 weeks. Two identical groups of 60 male and female mice each served as controls. The morphology and the incidence of neoplasms is described and compared with the tumor spectrum of other nucleoside analogues. Light microscopically, lobucavir-induced neoplastic lesions consisted of upper digestive tract squamous cell neoplasia in males and females; cervical, vaginal, and cutaneous squamous cell neoplasia in females; and Hardarian gland adenomas and adenocarcinomas in male mice. These results suggest that long-term administration of lobucavir causes neoplasia in mice, the spectrum of which resembles that observed after long-term administration of zidovudine or ganciclovir.     

Glucocorticoid effects on rabbit fetal lung maturation in vivo: an ultrastructural morphometric study.

Maternal administration of glucocorticoids is known to stimulate fetal lung maturation. In the present study, we used microscopy and stereology to evaluate the morphological effects of maternal glucocorticoid treatment on rabbit fetal lung tissue. Betamethasone was administered to pregnant rabbits on days 25 and 26 of gestation at a dose of 0.2 mg/kg body weight. The animals were sacrificed on day 27 of gestation. Glucocorticoid treatment significantly increased the presumptive airspace in the fetal lung tissue but did not alter the relative proportion of epithelium, connective tissue, or vasculature in the tissue. In addition, glucocorticoid treatment significantly increased the proportion of type II cells in the prealveolar epithelium, increased the rate of phosphatidylcholine synthesis, and increased the content of the major surfactant-associated protein, SP-A, in the fetal lung tissue. We could detect no effect of betamethasone on lamellar body cross-sectional area, numerical density, or volume density within fetal lung type II cells. Glucocorticoid treatment of the pregnant doe caused a decrease in the volume density of intracellular glycogen and an increase in the volume density of mitochondria in fetal lung type II cells. Betamethasone treatment did not alter the distance between fetal lung epithelial cells and subadjacent connective tissue cells. However, glucocorticoid treatment increased the number of connective tissue foot processes that pierced the epithelial basal lamina. Thus, glucocorticoid treatment of the pregnant doe results in structural changes in the fetal lung tissue, an acceleration of some aspects of type II cell differentiation, and a concomitant increase in epithelial-mesenchymal interactions.     

An antibody against hyperphosphorylated neurofilament proteins collapses the neurofilament network in motor neurons but not in dorsal root ganglion cells.

The carboxyl-terminal region of both the medium and high molecular weight neurofilament proteins contains repeated sequences that are sites for phosphorylation. The monoclonal antibody SMI31 specifically recognizes the conformation of these multiphosphorylated domains in an intermediate state of phosphorylation. Microinjection of SMI31 into living spinal motor neurons in culture resulted in a gradual collapse of the arrays of neurofilaments in perikarya and dendrites. In some cells, antibody-decorated filaments penetrated the axon and accumulated in proximal axonal segments causing their swelling. In dorsal root ganglion neurons, microinjected SMI31 bound to neurofilaments but did not induce collapse of the network or proximal axonal swelling. This study supports a role for phosphorylation of neurofilament sidearms in control of neurofilament transport and illustrates that interference with these sites has different consequences on neurofilament organization and morphology in different cell types.     

How much do 'attention' tests tell us?

Twelve measures commonly used to assess attentional processes were examined in a sample of 120 outpatients referred for neuropsychological evaluation. A single factor solution emerged. A second analysis partially replicated factors derived by Shum. McFarland, Bain, and Humphreys (1990). Classification rates (impaired vs. unimpaired) for the measures are presented. The implications of these findings for clinical assessment of attention are discussed     

Didanosine (ddl) and stavudine (d4T): Absence of peripheral neurotoxicity in rabbits

Some 20 male New Zealand White rabbits (five/group) were given either didanosine (ddl) or stavudine (d4T) at 750 and 1500 mg/kg body weight/day by oral intubation for 24 wk. An additional group was given 300 mg/kg body weight/day zidovudine (AZT) as a negative control. After 13 weeks the high dose of ddl was lowered from 1500 to 1000 mg/kg body weight/day following the death of one rabbit and continued inappetence in the dose group. The rabbits were observed daily, plasma drug levels were monitored, and electrophysiological measurements of peripheral nerve conduction were performed during the study. Additionally, body weight and food intake were recorded, and clinicopathological parameters were evaluated. Sections of selected peripheral nerves, and dorsal and ventral spinal nerve roots were examined by light and transmission electron microscopy. Although peripheral neuropathy has been reported in rabbits with the nucleoside analogue zalcitabine (ddC), based on clinical observations, electrophysiological measurements, and light and electron microscopy, no evidence of peripheral neurotoxicity was observed in rabbits given either ddl or d4T.