Schwann cell hyperplasia and tumors in transgenic mice expressing a naturally occurring mutant NF2 protein

Specific mutations in some tumor suppressor genes such as p53 can act in a dominant fashion. We tested whether this mechanism may also apply for the neurofibromatosis type-2 gene (NF2) which, when mutated, leads to schwannoma development. Transgenic mice were generated that express, in Schwann cells, mutant NF2 proteins prototypic of natural mutants observed in humans. Mice expressing a NF2 protein with an interstitial deletion in the amino-terminal domain showed high prevalence of Schwann cell-derived tumors and Schwann cell hyperplasia, whereas those expressing a carboxy-terminally truncated protein were normal. Our results indicate that a subset of mutant NF2 alleles observed in patients may encode products with dominant properties when overexpressed in specific cell lineages.     

The effects of antihypertensive therapy on left ventricular mass in elderly patients

Left ventricular mass sometimes decreases during treatment of hypertension, but this response is inconsistent and its effects on left ventricular function are unknown. In a six-month randomized trial, we studied the ability of verapamil and atenolol to reduce left ventricular mass in 42 elderly patients with hypertension and the effects of this reduction in mass on cardiac function. The mean blood pressure (+/- SE) decreased in both the group that received verapamil (from 171.4 +/- 3.2/93.0 +/- 2.5 mm Hg to 142.9 +/- 2.8/79.0 +/- 2.0 mm Hg) and the group that received atenolol (from 179.6 +/- 4.6/98.5 +/- 2.4 mm Hg to 148.1 +/- 3.3/83.4 +/- 1.2 mm Hg), but the atenolol-treated patients more frequently required the addition of chlorthalidone to achieve blood-pressure reduction (P less than 0.01). Verapamil resulted in a reduction in the left-ventricular-mass index from 104 +/- 5 g per square meter of body-surface area to 85 +/- 5 g per square meter (P less than 0.01). Atenolol did not produce a reduction in the left-ventricular-mass index (109 +/- 9 g per square meter before treatment vs. 112 +/- 10 g per square meter after treatment). Two weeks after the withdrawal of antihypertensive therapy, blood pressure returned to pretreatment values. Nevertheless, in patients whose left ventricular mass had decreased, two measures of diastolic filling, the peak diastolic filling rate to the peak ejection rate, were significantly higher than before treatment (2.42 +/- 0.2 vs. 3.31 +/- 0.4 [P less than 0.05] and 0.61 +/- 0.03 to 0.85 +/- 0.05 [P less than 0.05], respectively). Diastolic filling was unchanged in the group that had no reduction in left ventricular mass. Cardiac output and the ejection fraction at rest and during mild exercise were unchanged in both groups as compared with baseline values. We conclude that left ventricular mass can be reduced in elderly patients with hypertension and mild ventricular hypertrophy who receive antihypertensive therapy. Reduction occurs more frequently with verapamil than with atenolol therapy, increases diastolic filling, and does not impair systolic function.     

Brain regions and their dynamics in prospective memory retrieval: a MEG study.

We measured brain activity using magnetoencephalography in five participants during ongoing tasks that included prospective memory, retrospective memory, and oddball trials. Sources were identified in the hippocampal formation and posterior parietal and frontal lobes. Posterior parietal cortex activation had an earlier onset in the prospective memory condition than retrospective memory or oddball conditions, a higher level of theta activity in the retrospective condition, and higher levels of upper alpha in the prospective and oddball conditions. Activation of the hippocampal formation had a longer duration in the retrospective memory and prospective memory conditions than the oddball condition, but prominent alpha and theta band activity was present in all three conditions. We interpret the early (87 ms) onset of activity in parietal cortex as evidence for an initial noticing of appropriate conditions for a PM response. Hippocampal activity may reflect a subsequent memory search for the intended action.     

Heterogeneity in the ultrastructure of the mucous (goblet) cells of the rabbit palpebral conjunctiva

Aim: The purpose of this study was to assess objectively the ultrastructure of the secretory granules in rabbit conjunctival mucin‐producing ‘goblet’ cells. Method: The upper eyelids from five young adult dioestrous female rabbits were dissected out, stretched onto a cardboard support and prepared for transmission electron microscopy by repeated application of an isotonic two per cent glutaraldehyde fixative at room temperature. Post‐fixation treatment included osmium tetroxide and staining with uranyl acetate and lead citrate. Low magnification micrographs were taken of the goblet cells of the conjunctiva, printed at a magnification of approximately 6,000 and the number, size and features of the secretory granules assessed. Results: Across the entire palpebral conjunctiva of ail five rabbits, the majority of mucous cells displayed a goblet shape and the secretory granules were uniformly pale in staining. The average width of the goblet cells was 10.8 ± 1.1 μm and the diameter of the secretory granules was 0.82 ± 0.16 μm. However, in localised regions across the palpebral conjunctiva of two of the rabbits, some goblet cells were different in that the secretory granules had either a denser‐staining core, in which some of the granules were densely staining (while others were pale) or most of the granules were densely staining. These mucous cells had an average diameter of 10.3 ± 1.7 μm and the granule diameters averaged 0.88 ± 0.01 μm. For these abnormal goblet cells, inflammatory cells were found in their immediate vicinity. Occasionally, goblet cells were seen to be in the process of degranulation with associated apparent cell necrosis and the mucin granule diameter was close to 1 μm. Conclusions: The ultrastructure of the mucin‐containing secretory granules of the conjunctival mucous cells is not necessarily homogeneous in character and further attention needs to be given to the effects of localised inflammation in the tissue and to possible hormonal influences.