Characterization of gp 50, a major glycoprotein present in rat brain synaptic membranes, with a monoclonal antibody

Several cell lines secreting monoclonal antibodies (Mabs) against a major forebrain synaptic membrane (SM) glycoprotein, gp 50, have been raised. Western blots show that the Mabs react with a polypeptide doublet of Mrs 49 and 45 kDa. These polypeptides exist solely in a concanavalin A (Con A) binding form. Removal of the Con A receptors by digestion with endo-beta-N-acetylglucosaminidase H (endo H) lowers the Mrs of the glycoprotein doublet to 36.5 and 34 kDa. Western blots of 2D polyacrylamide gels indicate that gp 50 exists in several isoforms. Solid phase radioimmunoassay (RIA) and Western blots of brain subcellular fractions show the antigenic material to be concentrated in the SM fraction, but to be present in much lower amounts in synaptic junctions and postsynaptic densities. Gp 50 appears to be brain specific. Regional distribution studies show that it is present in all brain regions but is two-fold concentrated in cerebellum, brainstem and midbrain compared to forebrain. Immunocytochemical studies of several brain regions show that gp 50-like immunoreactivity is neuron specific and is concentrated in selected neuronal species, particularly granule cells. In both cerebellar and hippocampal granule cells gp 50-like immunoreactivity is localized in the perikarya and primary dendrites. Though immunocytochemistry did not show staining of synaptic regions this may be due to masking of the reactive epitope. The results are discussed in terms of the molecular properties of gp 50 and its subcellular localization in brain tissue.     

Sleep in Pick disease

19 polygraphic sleep recordings from 12 patients with Pick's Disease, including four histologically proved cases, were compared to those of an age-matched control group. Symptoms had been present for a mean 8 years, the patients being aged 59 to 78 (mean 70.5 years). All sleep stages could be identified. Total sleep time was reduced and the number of awakenings was sharply increased. High proportion of stage 1 contrasted with the reduction in the other sleep stages with disappearance of stage 4 in advanced cases. REM Sleep was identified in all recordings, although reduced as a function of the length of the illness; its production as a function of total sleep time was not different from that of the control. REM Sleep appeared often fragmented and with a remarkably short latency, reminiscent of that observed in severely depressed patients.     

Is herpes zoster a marker for occult or subsequent malignancy?

BACKGROUND: It has been suggested that herpes zoster may be a marker for occult malignancy. AIM: To examine the emergence of a subsequent cancer diagnosis in patients with and without herpes zoster. DESIGN OF STUDY: Retrospective cohort study. SETTING: Results were based on the database of Intego, an ongoing Belgian general practice-based morbidity registry, covering 37 general practitioners and including about 311 000 patient years between the years 1994 and 2000. METHOD: Survival analysis comparing the emergence of malignancy in patients with and without herpes zoster. RESULTS: The number of patients below the age of 65 years with herpes zoster, cancer or both was too low to draw any sensible conclusions. Above the age of 65 years we identified a significant increase of cancer emergence in the whole group and in females (hazard ratio = 2.65, 95% confidence interval = 1.43 to 4.90), but not in males. No difference could be identified in the first year after the herpes zoster infection. CONCLUSION: Our results do not justify extensive testing for cancer in herpes zoster patients. The association we identified, however, leaves open a number of questions with respect to the physiopathology behind it.     

The effects of severe visual challenges on steering performance in visually healthy young drivers.

PURPOSE: Two experiments explored the extent to which induced blur, reduced luminance, and reduced visual fields affect drivers' steering performance in a driving simulator. METHODS: In experiment 1, ten young participants (M = 21.2 years) drove at approximately 89 km/h (55 mph) along a curvy roadway while being exposed to blur (0 to + 10 D), luminance (0.003 to 16.7 cd/m), and visual field (1.7 and 150 degrees) manipulations. In experiment 2, a new group of ten young participants (M = 18.5 years) drove while exposed to seven visual field sizes (1.7 to 150 degrees). RESULTS: Steering was sensitive to a reduced field size but not to the blur and luminance challenges. Acuity, on the other hand, was sensitive to the blur and luminance challenges but not to reduced field size. DISCUSSION: In healthy young drivers, steering performance is remarkably robust to severe blur and to extremely low luminances. These results support a key element of the selective degradation hypothesis advanced by Leibowitz and colleagues--that steering abilities are preserved at night even when the ability to recognize objects and hazards is not. Additional research should address the other element of this hypothesis--that drivers fail to appreciate the extent to which their visual abilities are degraded at night.     

Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.     

Scanning electron microscopic study of degeneration and regeneration in the olfactory epithelium after axotomy

Summary The olfactory epithelium of the adult hamster (Mesocricetus auratus) was examined with the scanning electron microscope following olfactory nerve axotomy. Axotomy results in retrograde degeneration of mature olfactory neurons. Maximum degeneration was observed around day 4. During the degeneration period the epithelium consists primarily of supporting and basal cells. Microvillar columnar supporting cells were observed to have fine cellular processes extending from their lateral border to neighbouring cells. Supporting cells extended to the basal lamina where they terminated in foot-like processes of variable shapes (club, splay and hook). Basal cells which gave rise to new replacement olfactory neurons were observed near the basal lamina. They had a rough cellular surface covered with small granules and fine cellular extensions. Bowman's gland duct cells extended unbranched through the epithelium where they formed funnel duct openings covered with microvilli. During early recovery periods (5–30 days) the number of olfactory neurons in the lower epithelium region increased. We observed olfactory neurons with developing axon and dendritic processes. Specialized growth cone structures were seen at the tips. Olfactory neuron growth cones were elongated or club-shaped and had a ruffled membrane surface. Several thin filopodia extended from the growth cone and made contact with adjacent cells. At late recovery periods (35–120 days) there was a marked increase in the number of olfactory neurons within the middle and lower epithelium regions. Numerous dendritic processes extended to the epithelial surface and terminated in knob-like ciliated structures. Olfactory axons passed basally, forming small intra-epithelial bundles that penetrated the basal lamina then fasciculated into larger bundles within the lamina propria.This study provides detailed three-dimensional observations of the olfactory epithelium following neuron injury, and describes neural degenerative changes, replacement of olfactory neurons, development and maturation. In addition, we describe the structure and basal attachment of supporting cells and their glial-like relation with olfactory neurons.