Differential involvement of protein 4.1 family members DAL-1 and NF2 in intracranial and intraspinal ependymomas.

Ependymomas are malignant CNS neoplasms with highly variable biologic behavior, including a generally better prognosis for intraspinal tumors. Inactivation of the NF2 gene on 22q12 and loss of its protein product, merlin, have been well documented in subsets of meningiomas and ependymomas. DAL-1, a related tumor suppressor and protein 4.1 family member on 18p11.3, has also been recently implicated in meningioma pathogenesis, though its role in ependymoma remains unknown. Therefore, we evaluated 27 ependymomas (12 intracranial and 15 spinal) using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to determine NF2/merlin and DAL-1/DAL-1 status at the DNA and protein levels. Demonstrable NF2 and DAL-1 gene deletions were each detected in 6 (22%) ependymomas. All 5 merlin losses by IHC occurred in spinal ependymomas (P =.047), whereas 5 (71%) DAL-1-negative cases were intracranial (P =.185). The former result is consistent with prior observations that NF2 mutations are generally limited to spinal ependymomas. In contrast to meningiomas, simultaneous merlin and DAL-1 losses were not encountered. Our findings suggest that (1) NF2 and DAL-1 losses are involved in the pathogenesis of spinal and intracranial ependymoma subsets, respectively and (2) given the number of cases with no demonstrable losses, other cellular perturbations must also be critical for tumori-genesis.     

Synthesis and NMR-analysis of deuterated and tritiated cyclooctyl acetic acid

To increase the bio-availability of naturally occurring steroids, esterification of the 17-hydroxy position is a useful approach. Besides (branched) alkanecarboxylic acids¹) and cyclohexanecarboxylic acid²) also cyclooctyl acetic acid ( 1 ) was applied. To establish the biological fate of the cyclooctyl acetic acid part of steroids the tritiated molecule was synthesized (Figure 1). Cyclooctanone ( 3 ) was condensed with cyanoacetic acid³) and the resulting cyanide ( 4 ) was hydrolyzed to cyclooctenyl acetic acid ( 2a )⁴) which contained according to ¹H NMR and ¹³C NMR 20% of the isomeric 2b (¹H NMR (C²HCl₃): 5,58 ppm (t, CH of 2a ) and 5,63 ppm (br.s CH of 2b ) ¹³C NMR(C²HCl₃): 129,6 ppm (CH of 2a ) and 115,0 ppm (CH of 2b )).     

Activity of the cyclic depsipeptide emodepside (BAY 44–4400) against larval and adult stages of nematodes in rodents and the influence on worm survival

The present investigations deal with the activity of the cyclic depsipeptide emodepside (BAY 44-4400) against larval and adult stages of three rodent nematodes. While emodepside acts strongly against the adult stages of the rat nematodes Nippostrongylus brasiliensis and Strongyloides ratti, as well as against the mouse nematode Heligmosomoides polygyrus, its actions against the larval stages of these nematodes vary according to the species. Thus, emodepside is highly effective against the lung and intestine larval stages of N. brasiliensis and S. ratti. By contrast. the larval stages of H. polygyrus in the intestine are only partly affected by higher emodepside dosages.     

Norepinephrine applied in the paraventricular hypothalamic nucleus stimulates vasopressin release

The present experiments were designed to investigate the effect of norepinephrine (NE) applied directly in the area of the paraventricular nucleus (PVN) of the hypothalamus on arginine-vasopressin (AVP) release and blood pressure. A microinjection of 0.4 micrograms NE in the PNV produced a plasma AVP level of 26.3 +/- 5.3 pg/ml compared to 5.3 +/- 0.6 pg/ml in controls receiving dextrose (P less than 0.001). This rise was associated with blood pressure elevations varying between 10 and 13 mm Hg, lasting for about 5 min. Systemic injection of an antivasopressor AVP antagonist reversed or prevented the blood pressure rise induced by NE microinjection. The data suggest that locally applied NE in vasopressinergic neurons of the hypothalamus stimulates the release of AVP and induces an AVP-dependent rise in blood pressure.     

Differences in oral health status between institutionalized and non-institutionalized older adults

Differences in oral health status between independent and institutionalized adults have been difficult to interpret because the latter population is typically older and has a higher proportion of women, confounding any association between institutionalization and disease levels. We undertook an analysis of oral disease amongst institutionalized (n = 149) and non-institutionalized (n = 246) samples of older adults randomly selected from the population in East York, Ontario. When the confounding effects of age and gender were controlled by constructing 67 matched pairs, institutionalized people were more than twice as likely to be edentulous (OR = 2.17, 95% CI = 1.09-4.29). This association was confirmed using data from all subjects in a logistic regression model. Analysis of covariance of data from dentate subjects revealed that the institutionalized seniors had fewer filled teeth (P less than 0.05, controlling for age and sex), but there were no statistically significant differences in the number of teeth which were missing, decayed, or requiring extraction. These findings suggest that antecedent, sociodemographic factors prior to institutionalization are responsible for the higher probability of oral disease in this group of older adults.     

ITI implants with overdentures: a prevention of bone loss in edentulous mandibles?

Changes in the bone mineral content (BMC) of edentulous mandibles with osseointegrated ITI implants supporting overdentures were measured in vivo by dual-photon absorptiometry. The BMC measurements were performed 3 weeks postoperatively and at the 2-year follow-up visit. Measurements were made in the ITI site (anteriorly), the premolar region just behind the fixtures, and the standard site of the mandible for obtaining reference values of the age-related MBC loss. The increased function of the mandible after this treatment seems to cause a load-related bone formation that minimizes, or in some cases may counteract, the physiologic age-related BMC loss leading to osteoporosis.     

Relational and non-relational memory – electrophysiological correlates of novelty detection, repetition detection and subsequent memory

The dissociability of novelty detection in relational (RM) and non-relational memory (NRM) is currently under debate. To further address the time courses and underlying brain correlates of novelty detection, event-related potentials (ERPs) were analysed for encoding and retrieval on three memory tasks in healthy subjects. Spatial and non-spatial RM as well as NRM were assessed separately. The ERPs related to RM and NRM were dissociable for hits and correct rejections in an early and late time window. An early old/new effect was observed for NRM. A late old/new effect replicated the frequently reported recollection-associated old/new effect in terms of direction and amplitudes. Four different novelty types (spatial relational, non-spatial relational, horizontal non-relational and inverted non-relational) were examined. The P3a related to novelty detection differed in horizontal vs. inverted distractors in NRM, but not in spatial vs. non-spatial RM. ERPs for repetition detection (hits during retrieval) and also for subsequent hits (encoding phase) differed between RM and NRM. These findings are discussed in relation to potential brain correlates in RM and NRM during encoding and retrieval.