Blockade of inhibition in a pathway with dual excitatory and inhibitory action unmasks a capability for LTP that is otherwise not expressed

Long-term potentiation (LTP) can be readily elicited in a number of hippocampal pathways, but has not been seen in the dentate commissural pathway. The dentate commissural pathway is similar to the commissural/Schaffer collateral projection to CA1 except that it produces powerful inhibition that occurs nearly concurrently with the excitation. The present study evaluates whether this inhibition prevents the pathway from expressing LTP. Acute neurophysiological experiments were carried out in urethane anesthetized rats. To locally block inhibition in the dentate gyrus, a recording micropipette filled with 8 mM bicuculline was positioned in the dentate gyrus. A control saline-filled micropipette was positioned nearby. The commissural pathway was activated by stimulating electrodes in the contralateral CA3/CA4 region. Brief high-frequency stimulation of the commissural pathway reliably elicited LTP at the bicuculline electrode but not at the control electrode. This LTP required a threshold level of stimulation for its initiation, suggesting that like most other examples of LTP, the LTP in the commissural system depended upon activation of a voltage-dependent receptor. The high-frequency stimuli used to induce LTP produced an extracellular negativity at the bicuculline electrode that was not present at the control electrode. This negative potential was selectively blocked by ketamine and MK801, suggesting that the negative potential reflects N-methyl-D-aspartate (NMDA) receptor activation. Taken together, these results suggest that LTP is not normally expressed by the dentate commissural pathway because the simultaneous inhibition prevents the depolarization-related relief of Mg2+ blockade of the NMDA receptor.     

High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group

Forty-four of 50 adult patients with advanced soft-tissue sarcoma who had received previous chemotherapy were evaluable for response after treatment with DTIC. The therapeutic schedule consisted of DTIC 1.2 g/m2 infused over 20 minutes, and repeated every 3 weeks. There were 1 complete and 7 partial remissions (objective activity 18%, 95% C.I. 7%-29%), with a median duration of 8 weeks (range 5-19), with the complete remission lasting 1 yr. Hematologic toxicity was dose-limiting; W.H.O. greater than or equal to 3 values were observed for WBC in 36%, and for platelets in 26% of patients. The non-hematologic toxicity included nausea and vomiting (90%), a flu-like syndrome (49%), diarrhea (35%), pain in the infused vein (28%) and hypotensive episodes (4%). Intermittent high-dose DTIC is active in advanced soft-tissue sarcoma and should be considered for inclusion in combination regimens.     

Results of inpatient pediatric resuscitation

We retrospectively reviewed the results of 42 cardiopulmonary arrests occurring over 1 yr in the general ward of a pediatric hospital. These data were compared to those of a similar study done 10 yr previously in the same institution. Patients were divided into those having pure respiratory arrest and those who also had cardiac arrest. In the most recent series, overall 6-month survival was 17%; however, only 9% of the cardiac arrest patients survived. Ten years previously, the survival rate from cardiac arrest was 11%. In both series, pure respiratory arrest had a significantly better outcome than cardiopulmonary arrest, and predictors of nonsurvival were a duration of arrest greater than 15 min and the administration of more than one iv bolus of epinephrine. During the more recent series, sepsis and upper airway problems produced fewer arrests. There was one neurologically damaged survivor in each study period. Our study confirms that the outcome of pediatric cardiac arrest is poor when arrest occurs in the hospital.     

Protein synthesis at the synapse: developmental changes, subcellular localization and regional distribution of polypeptides synthesized in isolated dendritic fragments.

This study evaluated local protein synthesis in subcellular fractions of pinched-off dendrites (synaptodendrosomes) from different brain regions and at different developmental ages. Synaptodendrosomes were labeled with [35S]methionine and newly synthesized proteins were characterized by SDS-PAGE and phosphorimaging. The same set of approximately 30 cycloheximide-sensitive labeled bands was observed in synaptodendrosomes isolated from different brain regions, although the relative enrichment of some individual bands varied. Labeling of several major proteins was developmentally regulated, revealing three different patterns of variation. Subcellular fraction studies revealed that at least 10 labeled bands were enriched in synaptic junctions.     

Leukaemia incidence in Welsh children linked with low level radiation--making sense of some erroneous results published in the media.

A series of self-published epidemiological reports purporting to show a major excess risk of leukaemia in pre-school children living near the Irish Sea coast of Wales have been presented in the media as evidence of the harmful effects of low level radiation arising from Sellafield. The Welsh Cancer Intelligence and Surveillance Unit (WCISU), the body responsible for population-based cancer information in Wales, can provide insights into the validity of these reports, which appear to be a consequence of various mistakes. This raises important questions about the research governance of such reports and the communication of scientific findings via the mass media. Without suitable safeguards the media are in danger of promulgating misinformation.     

SEAT-BELT SYNDROME REVISITED

This report describes a complex syndrome of injuries occurring in a young female who was a back seat passenger wearing a lap-belt restraint in a high-speed road traffic accident. As a consequence of the forced flexion distraction injury of her lumbar spine, she sustained a fracture-subluxation of the first lumbar vertebra in association with a jejunal perforation and extensive small intestinal mesenteric laceration. She also had a large traumatic hernia of the anterior abdominal wall, which was overlooked at primary laparotomy. This report highlights collectively the classical combination of injuries associated with the lap-belt syndrome and demonstrates the importance of carefully inspecting the anterior abdominal wall for deficiencies, because traumatic herniation may be easily overlooked.     

Platelets of the Wistar Furth rat have reduced levels of alpha-granule proteins. An animal model resembling gray platelet syndrome.

Rats of the Wistar Furth (WF) strain have hereditary macrothrombocytopenia (large mean platelet volume [MPV] with increased platelet size heterogeneity and reduced platelet count). Ultrastructural studies suggest that this anomaly results from erratic subdivision of megakaryocyte cytoplasm into platelets. In this study, we have examined protein profiles of platelets of WF rats for biochemical abnormalities associated with this anomaly. Marked decreases in protein bands with an Mr of 185, 57, 53, 16, 13, and 8 kd were observed in one-dimensional reduced SDS-PAGE gels in WF platelets compared with platelets of Wistar, Long Evans, and Sprague-Dawley rats. These proteins were released into the supernatant when washed platelets were treated with thrombin suggesting that they were alpha-granule proteins. These abnormalities were not present in offspring of crosses between Wistar Furth and Wistar rats; however, they were present in platelets of offspring with large MPV derived from backcrosses of (WF X Wistar) F1 males to WF females, but not in backcross offspring with normal platelet size. Immunoblotting confirmed decreased levels of thrombospondin, fibrinogen, and platelet factor 4 in WF platelets. Electron microscopic examination revealed that platelet alpha granules were usually smaller in Wistar Furth than in Wistar rats. In addition, immunogold electron microscopy demonstrated that the surface connected canalicular system of the large Wistar Furth platelets, contained dense material composed of alpha-granule proteins, not present in Wistar platelets. From these results, we conclude that the Wistar Furth rat platelet phenotype of large mean platelet volume and decreased levels of alpha-granule proteins represents an animal model resembling gray platelet syndrome. The autosomal recessive pattern of inheritance of the large MPV phenotype and platelet alpha-granule protein deficiencies suggests that a component common to both formation of platelet alpha granules, and subdivision of megakaryocyte cytoplasm into platelets, is quantitatively or qualitatively abnormal in Wistar Furth rat megakaryocytes and platelets.