Superior colliculus and active navigation: role of visual and non-visual cues in controlling cellular representations of space

To begin investigation of the contribution of the superior colliculus to unrestrained navigation, the nature of behavioral representation by individual neurons was identified as rats performed a spatial memory task. Similar to what has been observed for hippocampus, many superior collicular cells showed elevated firing as animals traversed particular locations on the maze, and also during directional movement. However, when compared to hippocampal place fields, superior collicular location fields were found to be more broad and did not exhibit mnemonic properties. Organism-centered spatial coding was illustrated by other neurons that discharged preferentially during right or left turns made by the animal on the maze, or after lateralized sensory presentation of somatosensory, visual, or auditory stimuli. Nonspatial movement-related neurons increased or decreased firing when animals engaged in specific behaviors on the maze regardless of location or direction of movement. Manipulations of the visual environment showed that many, but not all, spatial cells were dependent on visual information. The majority of movement-related cells, however, did not require visual information to establish or maintain the correlates. Several superior collicular cells fired in response to multiple maze behaviors; in some of these cases a dissociation of visual sensitivity to one component of the behavioral correlate, but not the other, could be achieved for a single cell. This suggests that multiple modalities influence the activity of single neurons in superior colliculus of behaving rats. Similarly, several sensory-related cells showed dramatic increases in firing rate during the presentation of multisensory stimuli compared to the unimodal stimuli. These data reveal for the first time how previous findings of sensory/motor representation by the superior colliculus of restrained/anesthetized animals might be manifested in freely behaving rats performing a navigational task. Furthermore, the findings of both visually dependent and visually independent spatial coding suggest that superior colliculus may be involved in sending visual information for establishing spatial representations in efferent structures and for directing spatially-guided movements.     

Retropharyngeal pseudomeningocele after atlanto-occipital dislocation: report of two cases

OBJECTIVE AND IMPORTANCE: We report two cases of retropharyngeal pseudomeningocele after atlanto-occipital dislocation. This is rare, with only one other reported case in the literature. CLINICAL PRESENTATION: We report two patients who presented after blunt cervical and head trauma. Plain films revealed that each patient had atlanto-occipital dislocation. Subsequent magnetic resonance imaging revealed the delayed development of retropharyngeal pseudomeningocele. Concomitant hydrocephalus was noted in both patients. INTERVENTION: The surviving patient showed marked neurological improvement and resolution of his pseudomeningocele after ventriculoperitoneal shunting. CONCLUSION: For patients with closed head injuries who develop posttraumatic pseudomeningocele, we recommend cranial computed tomography to assess for the presence of hydrocephalus. In patients with atlanto-occipital dislocation, delayed neurological deterioration warrants magnetic resonance imaging of the craniocervical junction to rule out posttraumatic pseudomeningocele.     

A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease

Lipoprotein lipase degrades triglycerides in plasma and as a byproduct produces HDL particles. Genetic variation in lipoprotein lipase may therefore affect cardiovascular risk. We tested 9,214 men and women from a general population sample and 948 patients with ischemic heart disease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with noncarriers, female heterozygous probands had increased plasma triglycerides (delta = 0.23 mmol/liter), while HDL cholesterol was reduced in both female and male carriers (delta = 0.18 mmol/liter and delta = 0.11 mmol/liter, respectively). A similar phenotype was found in six homozygous carriers. On multiple logistic regression analysis, plasma triglycerides and HDL cholesterol were independent predictors of ischemic heart disease in both genders. On univariate analysis, odds ratios for ischemic heart disease in probands were 1.89 in women (95% CI: 1.19-3.01) and 0.90 in men (95% CI: 0.62-1.31), and on multivariate analysis were 1.98 in women (95% CI: 1.11-3.53) and 1.02 in men (95% CI: 0.65-1.60). This study demonstrates that a single common mutation in the lipoprotein lipase gene is associated with elevated plasma triglycerides and reduced HDL cholesterol levels, whereby carriers, in particular women, seem to be predisposed to ischemic heart disease. It cannot be excluded, however, that male carriers of this substitution may represent a subset of low-HDL individuals without raised triglycerides not predisposed to ischemic heart disease.     

Language dysfunction in children with Rolandic epilepsy

Rolandic epilepsy is regarded as the classic example of benign focal epilepsy. However, neuropsychological deficits have been noted in affected children. As Rolandic discharges are mainly distributed over the centrotemporal region, specific interference with language function might be suspected. Therefore, we conducted a standardized neuropsychological assessment in children with Rolandic epilepsy which covered all important aspects of language processing. We measured intelligence Quotient, verbal memory, auditory discrimination, vocabulary, grammar and literacy in 20 children with an active Rolandic focus. Information about performance at school was obtained from teachers by means of a questionnaire. Patients with Rolandic epilepsy failed five of the twelve standardized language tests significantly more often than the normative population and consequently showed impairment of the following functions: reading, spelling, auditory verbal learning, auditory discrimination with background noise and expressive grammar. Thirteen of the 20 children showed language dysfunction with difficulties in two or more of the twelve standardized language tests. In eight of these 13 children the Full Scale Intelligence Quotient was within average range, indicating a specific language deficit. Language dysfunction was closely associated with learning difficulties at school. This study documents a consistent pattern of language dysfunction in children with Rolandic epilepsy which suggests interictal dysfunction of perisylvian language areas.     

Mechanisms of resistance of human small cell lung cancer lines selected in VP-16 and cisplatin

BACKGROUND: The combination of VP-16 and cisplatin is one of the most active regimens available for the treatment of small cell lung cancer (SCLC), however, most tumors eventually become resistant to these drugs. METHODS: To investigate the problem of resistance to VP-16 and cisplatin in patients with SCLC, we established two resistant sublines from the drug sensitive human SCLC line, NCI-H209, by in vitro selection in VP-16 and cisplatin. RESULTS: The VP-16-selected cell line, H209/VP, was more than 100-fold resistant to VP-16, and displayed cross-resistance to VM-26 and other topoisomerase II interactive drugs, but not to vinca alkaloids. There was no difference in accumulation of VP-16 in H209/VP compared with its parent cell line. The level of topoisomerase II-alpha was reduced to 8% of that in the parent cell line, and there was an altered form of this enzyme with a molecular weight of 160 kilodaltons (kDa), in addition to the normal 170 kDa protein. The cisplatin-selected cell line, H209/CP, was 11.5-fold resistant to cisplatin, with only a low level of cross-resistance to other platinum compounds including carboplatin, tetraplatin, iproplatin, and lobaplatin. This line was highly cross-resistant to vinca alkaloids, but not to anthracyclines or epipodophyllotoxins. The H209/CP cell line was not resistant to cadium chloride, suggesting that alterations in metallothionein are unlikely to be a cause of resistance. Although glutathione (GSH) levels were increased nearly 2-fold in H209/CP, there was no difference in levels of the GSH-related enzymes glutathione-S-transferase, glutathione peroxidase, and glutathione reductase, compared with the parent line. The H209/CP line had a 1.4-fold elevation of topoisomerase II-alpha. The accumulation of cisplatin was reduced in this cell line, and there were fewer DNA-interstrand cross links formed in the presence of cisplatin in H209/CP, compared with the parent line. Neither H209/VP nor H209/CP expressed MDR1, the gene for P-glycoprotein. The MRP gene was expressed at a slightly higher level in the H209/VP cell line, but there was no significant increase in expression of this gene in the H209/CP cell line. CONCLUSIONS: The resistance of the H209/VP cell line is associated with an alteration of topoisomerase II-alpha, whereas the resistance in the H209/CP line is associated with reduced drug accumulation.     

Dopamine release in the nucleus accumbens by hypothalamic stimulation-escape behavior

It is known that lateral hypothalamic stimulation or self-stimulation can release dopamine in the nucleus accumbens (NAc). The present experiment illustrates that an aversively motivated behavior can also do this. Rats were prepared with microdialysis probes in the NAc and electrodes in the lateral hypothalamus (LH) or medial hypothalamus (MH). Automatic stimulation of the LH increased extracellular dopamine in the NAc 30% as reported earlier. The animals would perform both self-stimulation to turn the current on and stimulation-escape to turn it off, suggesting a combination of reward and aversion. Escape responding increased extracellular dopamine (DA) 100%, even though there was less total stimulation. Automatic stimulation of the MH did the opposite of the LH by decreasing accumbens dopamine (-20%), and the animals would only perform stimulation-escape, indicative of pure aversion. But again, extracellular DA in the NAc increased 100% during escape responding. Thus DA can be released during negative reinforcement when an animal's behavior is reinforced by escape from lateral or medial hypothalamic stimulation. This suggests that DA release was correlated with stimulation-escape behavior, rather than the aversiveness of automatic stimulation.     

Estimates of fatal child abuse and neglect, United States, 1979 through 1988

The results of recent surveys in the United States have suggested a rising tide of fatalities due to child abuse or neglect (CAN). Because these surveys lack consistency in case definition and are incomplete in coverage, the use of death certificate data to estimate the number of CAN deaths was explored. To estimate these deaths among children 0 through 17 years old for 1979 through 1988, three models were formulated, each comprising six coding categories: (1) deaths coded explicitly as due to CAN, (2) homicides, (3) injury deaths of undetermined intentionality, (4) accidental injury deaths, (5) sudden infant death syndrome fatalities, and (6) natural-cause deaths. Research studies and crime data were relied on to estimate the proportions of deaths in categories 2 through 6 that were actually due to CAN, and other assumptions were varied to create a range of estimates. For the 10-year period, the estimated mean annual CAN fatalities ranged from 861 to 1814 for ages 0 through 4, and from 949 to 2022 for ages 0 through 17. Child abuse and neglect death rates did not increase over the period; in fact, they were relatively stable for ages 0 through 17 and showed a modest decline for 0 through 4. Ninety percent of fatal CAN occurs among children younger than 5 years old, and 41% occurs among infants. About 85% of CAN deaths are recorded as due to other causes.(ABSTRACT TRUNCATED AT 250 WORDS)     

The successful induction of molting in the adult male lobster (Homarus americanus) with a slow-release form of ecdysterone

In an initial, and then a confirmatory experiment, adult, male lobsters were injected with solvent, ecdysterone (E, 2.0 mug/g live weight) or ecdysterone acetate (EAc, 2.5 or 5.0 mug/g live weight) emulsions in Freund's incomplete adjuvant (FIA). Control lobsters underwent no molts and only one death in the two cases. The E treated animals all died (average: exp. 1, 19.2 +/-2.1 days; exp. 2, 25.3 +/- 8 days). After the lobsters were treated twice with 2.5 mug EAc/g live weight, in the first experiment, four out of five molted and one died; in the second experiment six out of eight molted, one died and one remained refractory. The high EAc dose resulted in five deaths, one molt and two pseudomolts after one treatment. It is concluded that the use of the oil emulsion and EAc sufficiently slowed the release of free ecdysterone to allow complete premolt development in the lobster.