Effects of inorganic and triethyl lead and inorganic mercury on the voltage activated calcium channel of Aplysia neurons.

Using conventional two electrode voltage clamp techniques we have studied the effects of Pb2+, triethyl lead (TEL) and Hg2+ on voltage-activated calcium channels of Aplysia neurons and found that all three metals are potent inhibitors at micromolar concentrations. However, the time course of current reduction or block and its reversibility vary when comparing Pb2+ to TEL and Hg2+. With application of Pb2+ the calcium current decreases immediately and a steady state is reached within three to seven minutes, depending upon the concentration of Pb2+ (IC50 = 61 microM). The block was easily reversed upon wash out of Pb2+ with a time course similar to that of onset. Perfusion with either TEL (5 to 50 microM) or Hg2+ (5 to 200 microM) resulted only in a small reduction of current when the substances reached the cell membrane but with clear reduction within 2 min. The decrease continued at about the same speed for the total duration of the application. Upon washing there was no recovery of the response. At the onset of washing the rate of current decline stopped for several minutes, but then the current continued to decline at a slower rate in the absence of toxicant. Our data suggest that Pb2+ acts by a direct and reversible blockade of the calcium channel. In contrast TEL and Hg2+ act slowly and irreversibly to block calcium channels at concentrations which do not greatly affect membrane potential or resistance. In spite of the slow time course these substances are probably acting directly on the calcium channel.     

Gingival cyst of the adult. Case report of a bilateral presentation

The gingival cyst of the adult (GCA) constitutes a pathologic developmental process that the dentist must be prepared to diagnose and treat. The GCA has been infrequently reported in the past as a unilateral phenomenon, but this case constitutes the first known report of synchronously occurring, bilateral GCA in the dental literature.     

The heterogeneity of the long-term course of schizophrenia

Research has demonstrated considerable heterogeneity in the long-term course of schizophrenia. In the period preceding the onset of frank psychosis (onset), patients vary relative to the rapidity of onset, the presence or absence of associality, and the presence or absence of semipsychotic symptoms. Following the onset of psychosis (middle course), patients may suffer from episodic or unremitting psychosis, and may or may not exhibit the deficit syndrome. In late adult life (late course), patients vary relative to the presence or absence of an improvement in psychosis and social capability. The usual approach to the study of putative course subtypes is to define a subtype by a number of features; they may include features of more than one epoch. In addition, the course of psychosis has not been distinguished from enduring personality impairments in these subtypes. Another approach to defining putative course subtypes would be based on dichotomizing patients according to the presence or absence of a particular feature of a single epoch. This second approach has important advantages: the availability of larger study populations and a diminished liability for confounding due to the correlates of features other than those under scrutiny.     

Magnetic resonance imaging of angiographically occult runoff vessels in peripheral arterial occlusive disease.

BACKGROUND. Bypass grafting to arteries of the lower leg has become standard surgical management of advanced peripheral vascular disease. Its success depends on identifying suitable distal vessels. Preoperative preparation includes imaging of the arteries of the lower leg, usually by conventional contrast arteriography. An alternative procedure, magnetic resonance (MR) angiography, has been successfully employed in patients with various cardiovascular diseases, but its possible value in patients with peripheral vascular disease has received little attention. METHODS. We used both conventional and MR angiography in preoperative studies of the lower-leg vessels of 23 patients (25 legs) with peripheral arteriosclerosis and arterial insufficiency, and developed independent therapeutic plans based on the information provided by each technique. When the plans differed, the interventional procedure judged more likely to save the limb was performed. The findings of conventional and MR angiography were verified by intraoperative arteriography, postinterventional arteriography, or direct operative exploration. RESULTS. MR angiography detected all vessels identified by conventional angiography, whereas conventional arteriography failed to detect 22 percent of the runoff vessels identified by MR angiography. The detection by MR angiography of vessels not identified by conventional angiography altered the surgical management of the disorders of four patients (17 percent) and guided successful bypass procedures. CONCLUSIONS. MR angiography is a noninvasive technique with greater sensitivity than conventional contrast arteriography for detecting distal runoff vessels in patients with peripheral arterial occlusive disease.     

Elevated membrane association of phospholipase C-gamma 1 in MDA-468 mammary tumor cells.

We have examined the distribution of phospholipase C-gamma 1 (PLC-gamma 1) between membrane and cytosolic fractions in several cell lines. In MDA-468 cells, which are derived from a human breast tumor, greater than one-half of the total PLC-gamma 1 is associated with the membrane fraction of the cell. Unlike the situation in A-431 cells [G. Todderud, M. I. Wahl, S. G. Ree, and G. Carpenter, Science, 248: 296-298, 1990], epidermal growth factor (EGF) stimulation of MDA-468 cells does not result in significantly increased PLC-gamma 1 association with membranes. Immunoblot analysis reveals low levels of phosphotyrosine in PLC-gamma 1 and EGF receptors in unstimulated MDA-468 cells and greatly increased phosphotyrosine levels in these proteins as a result of EGF stimulation of the cells. We conclude that autocrine activation of EGF receptors is not responsible for the elevated association of PLC-gamma 1 with membranes in these cells.     

Synthesis and transport of GAP-43 in entorhinal cortex neurons and perforant pathway during lesion-induced sprouting and reactive synaptogenesis.

Metabolic labeling and quantitative 2D gel autoradiography were used to assess changes in the synthesis and transport of GAP-43 in entorhinal cortex (EC) neurons and perforant pathway during lesion-induced sprouting and reactive synaptogenesis. In normal adult rats, there is a high constitutive level of GAP-43 synthesis and transport in EC neurons projecting to the hippocampus. Following unilateral EC lesions, there is a 2-fold (100%) increase in the transport of newly synthesized GAP-43 to the contralateral or 'sprouting' hippocampus. The timing of this upregulation (between 6 and 15 days) suggests that changes in GAP-43 expression occur in response to the growth of presynaptic terminals during sprouting.     

Statistical issues in long-term followup studies

The thesis of this article is that since followup studies of patients with schizophrenia have provided a rich body of informative knowledge, emphasis should now be on hypothesis testing in future studies. The consumer of research needs to have a general appreciation of statistical thinking, design, and methods to make an informed synthesis of results presented. This article presents a brief discussion of relevant statistics and statistical issues, as free of jargon as possible. Given the multivariable nature of psychiatric research, the natural focus is on multivariate statistics. A strong background in statistics is not required to understand the methods described and how and why they might be applied. Reference material for more detailed discussions is provided. It is a truism to say that the highest quality scientific work is dependent on an intimate collaboration with the expert in statistics and the expert in clinical methods, and this merits repeating only because it is so often ignored.     

Effect of training frequency and specificity on isometric lumbar extension strength

To investigate the effects of training frequency and specificity of training on isolated lumbar extension strength, 72 men (age = 31 +/- 9 years) and 42 women (age = 28 +/- 9 years) were tested before and after 12 weeks of training. Each test involved the measurement of maximum voluntary isometric torque at 72 degrees, 60 degrees, 48 degrees, 36 degrees, 24 degrees, 12 degrees, and 0 degrees of lumbar flexion. After the pretraining tests, subjects were randomly stratified to groups that trained with variable resistance dynamic exercise every other week (1X/2 weeks, n = 19), once per week (1X/week, n = 22), twice per week (2X/week, n = 23) or three times per week (3X/week, n = 21); a group that trained isometrically once per week (n = 14); or a control group that did not train (n = 15). Analysis of covariance showed that all training groups improved their ability to generate isometric torque at each angle measured when compared with controls (P less than 0.05). There was no statistical difference in adjusted posttraining isometric torques among the groups that trained (P greater than 0.05), but dynamic training weight increased to a lesser extent (P less than 0.08) for the 1X/2 weeks group (26.6%) than for the groups that trained 1X/week, 2X/week, and 3X/week (37.2 to 41.4%). These data indicate that a training frequency as low as 1X/week provides an effective training stimulus for the development of lumbar extension strength. Improvements in strength noted after isometric training suggest that isometric exercise provides an effective alternative for developing lumbar strength.