Spatial learning and memory following fimbria-fornix transection and grafting of fetal septal neurons to the hippocampus

Summary The ability of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in developing cholinergic neurons, to ameliorate cognitive impairments induced by bilateral fimbria-fornix transections in rats was examined in three experiments using the Morris water-maze to test different aspects of spatial memory. Experiment 1. Rats with fimbria-fornix lesions received either septal cell suspension grafts or solid septal grafts; normal rats and rats with lesions alone were used as controls. Sixteen weeks after surgery, the rats' spatial learning and memory were tested in the water-maze using a place test, designed to investigate place navigation performance, in which rats learned to escape from the water by swimming to a platform hidden beneath the water's surface. After 5 days of training, the rats were given a spatial probe test in which the platform was removed from the tank to test spatial reference memory. Experiment 2. The same rats used in Exp. 1 were tested in a delayed-match-to-sample, working memory version of the water-maze task. The platform was located in one of two possible locations during each trial, which was composed of 2 swims. If the rat remembered the location of the platform on the 2nd swim of a trial, it should find the platform more quickly on that swim, and thereby demonstrate working memory. Experiment 3. Prior to receiving fimbria-fornix lesions, normal rats were trained in a modification of the water-maze task using alternating cue navigation and place navigation trials (i.e., with visible or non-visible escape platforms). The retention and reacquisition of the place task and the spatial probe test were examined in repeated tests up to 6 months after the lesion and intrahippocampal grafting of septal cell suspensions. The effects of central muscarinic cholinergic receptor blockade with atropine were also tested. Normal rats performed well in both the place and spatial probe tests. In contrast, rats with fimbria-fornix lesions only were unable to acquire or retain spatial information in any test. Instead, these rats adopted a random, nonspatial search strategy, whereby their latencies to find the platform decreased in the place navigation tasks. Sixty to 80% of the rats with septal suspension or solid grafts had recovered place navigation, i.e., the ability to locate the platform site in the tank, in Exp. 1 and 3, and they showed a significantly improved performance in the working memory test in Exp. 2. Atropine abolished the recovered place navigation in the grafted rats, whereas normal rats were impaired to a lesser extent. In contrast, atropine had no effect on the non-spatial strategy adopted by rats with fimbria-fornix lesions only. The results show that: (1) fimbria-fornix lesions disrupt spatial learning and memory in both naive and pretrained rats; (2) with extended training the fimbria-fornix lesioned rats develop an efficient non-spatial strategy, which enables them to reduce their escape latency to levels close to those of intact controls; (3) intrahippocampal septal grafts can restore the ability of the lesioned rats to use spatial cues in the localization of the platform site; and (4) the behavioural recovery produced by grafts is dependent upon an atropine sensitive mechanism.     

Japanese encephalitis virus glycoproteins

Mature Japanese encephalitis (JE) virus, or N-form virus, contained three structural proteins: V-1, V-2, and V-3. The large membrane protein V-3 was glycosylated, whereas both V-1 (the small membrane protein) and V-2 (the nucleocapsid protein) were not. Intracellular (I-form), immature virions from infected chick embryo cells did not contain V-1 but a larger protein NV-2, which was glycosylated. T-form virions, released by LLC-MK₂ cells incubated with tris(hydroxymethyl)amino-methane (Tris), also contained the glycoprotein NV-2 instead of the nonglycosylated and smaller V-1. We therefore concluded that JE contained two structural membrane glycoproteins, at least one of which is modified during morphogenesis. The NV-2 polypeptide was heterogeneous, and slight differences in electrophoretic mobility were detected among the NV-2 polypeptide peaks from glucosamine-labeled I-form and T-form virions, glucosamine-labeled cell extracts, and amino acid-labeled cell extracts. The significance of these differences is not clear, but they may indicate that NV-2 is composed of several proteins of similar molecular weight. By analyzing extracts of infected cells labeled with glucosamine or amino acids, we tentatively classified the intracellular polypeptide NV-3 as a virus-specified nonstructural glycoprotein; this polypeptide may be a proteolytic fragment of V-3. The virus-specified polypeptides NV-5, NV-4, and NV-1 were classified as nonglycosylated, nonstructural proteins.     

A longitudinal study of sleep stages in young women during pregnancy and postpartum.

We conducted a longitudinal polysomnographic study in five healthy primiparous subjects, whose sleep was first recorded between 8 and 16 weeks of gestation, then every 2 months until parturition and at 1 month postpartum. The first 6 hours of sleep were used for statistical analysis. In contrast to previous studies, we found no reduction in stage 4 sleep with pregnancy. Slow-wave sleep (comprising stages 3 and 4), was significantly higher at 27-39 weeks of gestation than at 8-16 weeks, as predicted by the restorative theory of sleep. There was no significant difference in rapid eye movement (REM) sleep time. When compared to a group of normal ovulating women, however, REM sleep time decreased during the last two months of pregnancy and, although there was no change in sleep onset latency, the time spent awake during the first six hours of sleep was increased. Future research into the effects of cortisol and progesterone is indicated.     

Relaxation therapy for hypertension: setting-specific effects.

We determined the effect of relaxation therapy for hypertension in patients whose blood pressure remained elevated despite the use of antihypertensive medication. The effect was assessed in multiple settings, including the relaxation therapist's office, the Hypertension Clinic, and the patient's natural environment, the latter using 24-hour automated ambulatory blood pressure measures. Nineteen patients were randomized either to temperature biofeedback-assisted relaxation or to an attention control, "stress education." Antihypertensive medication was kept constant. In the behavioral therapist's office, blood pressure decreased in equivalent amounts with both treatments. Hypertension Clinic nurse blood pressure remained stable or increased with both treatments, but again there was no difference between treatments. Ambulatory blood pressure increased with relaxation therapy and decreased with stress education, the effect being significant for diastolic pressure. The effects on ambulatory blood pressure were limited to the waking hours. The only variable that showed superior effects for relaxation therapy was physician-determined blood pressure. These results call into question the generalizability of the effects of relaxation therapy from one setting to another.     

Effects of albuterol and procaterol on exercise-induced asthma

Procaterol and albuterol, beta agonists, were studied using a placebo-controlled, repeated exercise challenge design in order to assess their duration of effectiveness in both bronchodilation and in modifying exercise-induced asthma (EIA). Fifty-three subjects aged 12 to 50 years who had at least a 20% drop in FEV1 during a screening exercise tolerance test were entered. Subjects took two inhalations of procaterol (10 micrograms/inhalation), albuterol (90 micrograms/inhalation), or placebo. Thirty minutes later they exercised on a treadmill at a workload sufficient to induce greater than or equal to 80% aerobic O2 consumption for six minutes. Pulmonary function was measured before and serially for 30 minutes after exercise. The same exercise challenge was repeated three, six, and nine hours after drug administration. Both procaterol and albuterol bronchodilated and modified EIA at 30 minutes and three hours, mean drops in FEV1 being 8.2 and 9.7% respectively at 30 minutes and 16.8 and 16.3% at three hours. This was compared with placebo falls of 30% and 26%. At six hours the subjects' response was similar after both procaterol and albuterol, and fewer subjects had a 20% fall in FEV1 than with placebo, although protection afforded by both beta agonists was substantially less than at three hours. Both drugs were tolerated well.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Surgical treatment of cardiac pheochromocytomas

The development at our institution of the radiopharmaceutical 131-I-metaiodobenzylguanidine has permitted for the first time scintigraphic localization of pheochromocytomas. By the use of this scan in combination with contrast-enhanced computed tomography, intrapericardial pheochromocytomas have been demonstrated in eight patients at our hospital during the past 2 years. Four of these patients have been operated upon by us, and each was found to have a pheochromocytoma arising from the heart (left atrium in three and interventricular groove at the aortic root in one). While in one patient it was possible to "shell" the tumor away from the left atrial wall without cardiopulmonary bypass, in the remaining patients, bypass and cardioplegia were required to resect the pheochromocytomas without inducing life-threatening intraoperative hypertension and cardiac arrhythmias. One patient required coronary artery reconstruction and two, excision of the posterior left atrial wall with pericardial replacement. One of these latter two patients died intraoperatively of uncontrollable hemorrhage. The three remaining patients are well and normotensive after more than 1 year of follow-up. Cardiac pheochromocytomas should not be approached as typical posterior mediastinal tumors, or as they are in the abdomen, with the expectation that they will "shell away" from contiguous structures. Cardiopulmonary bypass should be available, and resection of involved myocardium may be necessary for complete removal.     

Social support and life events in working class women. Stress buffering or independent effects?

Several authors have suggested that social support reduces the risk of psychiatric disorder by providing a "buffer" against the adverse effects of stressful events. Others have proposed, in contrast, that social support is beneficial irrespective of life stress. We addressed this issue in a community survey of 193 working class mothers by measuring social support, threatening life events, psychiatric symptomatology, and psychological well-being via a detailed assessment combining a standardized interview and case-identification procedure with self-report questionnaires yielding continuous measures of distress and well-being. Subject selection minimized confounding between support and events. The effects of life stress and social support were found to be largely independent of one another, although detailed analysis suggested that the conclusions drawn in such studies are affected by the measures and statistics used.