Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

The effects of inversion and eye displacements of familiar and unknown faces on early and late-stage ERPs.

OBJECTIVES: The objective of this study is to examine whether configural alterations of faces affect early or late processing stages as a function of their familiarity and their level of representation in memory. We then sought to verify whether the structural encoding stage is susceptible to top-down influences. METHODS: Electrophysiologic and behavioral studies were undertaken, during which unknown and familiar faces were presented upright or upside-down with or without feature alterations. The subjects were asked to determine whether the faces were familiar or not. RESULTS: N170 and N360 amplitudes were larger for familiar faces as well as altered ones. A higher degree of familiarity decreased reaction times (RTs) and N360 latencies, but increased N170 latencies, whereas face alterations increased RTs and latencies of both components examined. However, familiarity interacted with altered face configurations only for RTs and the N170. SIGNIFICANCE: In the perceptual stage, familiar faces seem to develop a more elaborate type of processing because of top-down influences linked to the robust nature of their representations in memory. The more elaborate type of processing for familiar faces has advantageous consequences for the following steps of information processing, by facilitating access to structural representations in memory (N360) as well as the final step reflected by RTs. The fact that configural alterations cause different effects for familiar as opposed to unfamiliar faces indicate that these stimuli are processed in a qualitatively different manner and solicit different representations in memory.     

The glycemic index of some foods common in Mexico

To investigate the increase of glycemia due to the ingestion of usual food in Mexico, portions with 50 g of carbohydrate form white corn tortilla, yellow corn tortilla, spaghetti, rice, potatoes, beans brown and black, nopal (prickle pear cactus) and peanuts, compared with white bread, were given to 21 healthy and 27 non-insulin-dependent diabetic subjects. Serum glucose and insulin were measured every 30 min for 180 min long. Glycemic index was obtained as: (area under curve of glucose with test food/area under curve of glucose with white bread) X 100. A corrected index was calculated subtracting the area corresponding to initial values. Insulin index was obtained similarly. Each sample was studied 14-18 times. Glycemic and insulin indexes of white and yellow corn tortilla, spaghetti, rice and potatoes were not different from bread (P greater than 0.05). Corrected glycemic indexes of brown beans (54 +/- 15, +/- SE) and black beans (43 +/- 17) were low (p less than 0.05), as well as corrected insulin indexes (69 +/- 11 and 64 +/- 10 respectively, (P less than 0.02). Peanuts had low glycemic (33 +/- 17, P less than 0.01), but normal insulin index. Nopal had very low glycemic and insulin indexes (10 +/- 17 and 10 +/- 16, P less than 0.0001). These data might be useful in prescribing diets for diabetic subjects.     

Adaptive modifications of postural attitude in conditions of weightlessness

Summary Adaptation of static posture was studied before, during, and after a 7-day space flight. Body segment orientations, body stability, and muscle activity underlying the reproduction of several postural attitudes were examined in various visual situations either with the shoes attached to the floor or during free floating. In standing or relaxed subjects whose shoes were attached to the floor, the tonic activity of the ankle flexor was enhanced relative to that in the same posture on earth, whereas the extensor activity disappeared. Errors in attempting to reproduce the normal terrestrial upright posture and a forward-leaning posture were accompanied by major changes in the synergies between neck, hip, knee, and ankle joints. These changes are mainly attributed to cumulative adjustments in response to nonvestibular signals such as tactile, articular, and proprioceptive cues.     

Detection of mouse IgE by CELISA

The detection and quantitation of mouse IgE is usually impaired by the difficulty to obtain reliable antibody reagents which are fully specific for the epsilon chain - and reactive enough - to be used in an enzyme-linked immunosorbent assay (ELISA). An ELISA on cells (CELISA) was developed for the detection of mouse IgE, using rat basophilic leukemia (RBL) cells. It is based on the high affinity of the receptors for the Fc of IgE (Fc epsilon R) displayed on the surface of the RBL cells. Since the epsilon chain specific recognition is achieved by the biological receptor of IgE, the detection of cell-bound IgE does not need the use of epsilon chain specific antibodies. Instead, one can use any enzyme-coupled antibody capable to recognize the IgE through its light-chain epitopes. Interestingly, when the IgE bound to the RBL cells has a known specificity, it can be detected through its paratopes using the cognate antigen coupled to an enzyme.     

Cytoprotective effect of vitamin A and its clinical importance in the treatment of patients with chronic gastric ulcer

The effects of vitamin A were studied on the basal and maximal gastric secretory responses of 12 patients; and on healing in 60 patients with chronic gastric ulcer. The effect of vitamin A on ulcer healing was evaluated by a multiclinical, multicentre, randomized, prospective study in which the patients were divided into three groups. In group A the patients were treated with antacids only; in group B the patients were given antacids plus vitamin A (in doses of 3 X 50.000 U orally); and in group C the patients received antacids, vitamin A plus cyproheptadine (in doses of 3 X 4 mg orally). The treatment lasted four weeks. At the beginning and the end of treatment endoscopies were performed and ulcer sizes were measured planimetrically. Various other parameters such as ulcer index, antacid consumption and laboratory parameters were also evaluated during the four-week treatment. It was observed that: (i) vitamin A (given in doses of 100.000 U i.m.) decreased neither basal nor maximal gastric secretory responses; (ii) the number of patients with completely healed gastric ulcer was significantly higher (P less than 0.05) in groups B and C than in group A; (iii) the extent of ulcer reduction was significantly higher (P less than 0.01) in groups B and C than in group A; (iv) no significant changes were observed in ulcer index and antacid consumption during the four-week treatment in the different groups of patients; (v) the reduction of ulcer size was significantly greater (P less than 0.01) in the group treated with antacids plus vitamin A than in the group treated with antacids only, at two weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dry heat loss in incubator: comparison of two premature newborn sized manikins

Keeping premature newborns warm is crucial for their survival. Their ability to prevent excessive heat loss to the environment and to control their body temperature is limited. The risk of hypothermia is particularly important for low-birth-weight newborns with a large body surface area in relation to their mass of heat-producing tissues. The present study was performed to assess the body heat loss difference between small and large body-size premature newborns using two anthropomorphic thermal manikins of premature newborns of 900 g and 1,800 g (respective body surface areas of 0.086 and 0.150 m²). The dry heat loss from the six body segments of the small manikin (S) was measured and compared with that of the large manikin (L). The two manikins were exposed to five different environmental temperatures ranging between 29 and 35°C in a single-walled, air-heated closed incubator. The magnitudes of heat loss decreased significantly by 20.4% between the two manikins [small manikin 110.1 (44.3) W/m² vs large manikin 87.6 (25.8) W/m², mean values with one standard deviation]. The results obtained from the comparison of the heat loss measures from the two manikins confirm the fact that the heat loss increases with an increase in the ratio of the body surface area to body mass. The thermal manikin appears to provide an accurate method for the assessment of thermal conditions in neonatal care.     

Behavioral and neurochemical effects induced by subchronic combined exposure to toluene at 40 ppm and noise at 80 dB-A in rats

We investigated whether exposure to noise, in addition to its well-known potentiating effect on toluene-induced ototoxicity, may also exacerbate behavioral disturbances and brain neurochemical alterations produced by subchronic exposure to low toluene concentration. To test this hypothesis, we evaluated whether subchronic combined exposure (16 weeks, 104 h per week) to noise at 80 dB-A and toluene at 40 ppm potentiates the recently reported neurotoxic effects of subchronic exposure to 40 ppm toluene. Locomotor and rearing activities, sensitization to narcosis induced by acute toluene at high concentration, and tyrosine and tryptophan hydroxylase activities in the caudate-putamen and hippocampus were investigated in both male and female rats. Our results confirm that subchronic exposure to 40 ppm toluene significantly decreases rearing activity and leads to a sensitization to toluene-induced narcosis, as evaluated by loss of righting reflex, but fails to demonstrate any adverse effect of noise, alone or in combination with toluene. Given that toluene has addictive properties, the lack of potentiating behavioral and neurochemical effect of noise is discussed with regards to a recent study that has shown that methamphetamine neurotoxicity is potentiated by exposure to loud noise.     

Physical activity improves gaze and posture control in the elderly

Ageing is associated with a decrease in the quality of balance regulation, in particular through dysfunctions of gaze control and postural stabilization, which results in an increased risk of falling. Conversely, the practice of physical and sporting activities has been shown to improve every level of postural regulation. This study is to assess the effects of the practice of physical activities on vestibulospinal reflex and ocular movements of visual and vestibular origins in elderly people. Gaze control and posture stabilization were evaluated in 13 healthy aged women who regularly practised physical activities and in 13 healthy aged sedentary women of a similar age, by dynamic posturographic test with electromyography, as well as electronystagmography with caloric and rotational vestibular tests, ocular saccades, smooth pursuit and optokinetic tests. The gaze and posture control performance of the active group was better; the proprioceptive and vestibular sensitivities were higher, visual detection quality was good, and reaction time was low. Regular physical activity develops or maintains the efficiency of the reflexes involved in postural control, especially through adequate neurosensorial information, which allows the central integrative structures to generate a more appropriate motor response.     

Hypoxia promotes murine bone-marrow-derived stromal cell migration and tube formation

Recent evidence indicates that bone-marrow-derived stromal cells (MSCs) have a histology coherent with endothelial cells that may enable them to contribute to tumor angiogenesis through yet undefined mechanisms. In this work, we investigated the angiogenic properties of murine MSCs involved in extracellular matrix degradation and in neovascularization that could take place in a hypoxic environment such as that encountered in tumor masses. MSCs were cultured in normoxia (95% air and 5% CO(2)) or in hypoxia (1% oxygen, 5% CO(2), and 94% nitrogen). We found that hypoxic culture conditions rapidly induced MSC migration and three-dimensional capillary-like structure formation on Matrigel. In vitro, MSC migration was induced by growth-factor- and cytokine-enriched conditioned media isolated from U-87 glioma cells as well as from MSCs cultured in hypoxic conditions, suggesting both paracrine and autocrine regulatory mechanisms. Although greater vascular endothelial growth factor levels were secreted by MSCs in hypoxic conditions, this growth factor alone could not explain their greater migration. Interestingly, matrix metalloproteinase (MMP)-2 mRNA expression and protein secretion were downregulated, while those of membrane-type (MT)1-MMP were strongly induced by hypoxia. Functional inhibition of MT1-MMP by a blocking antibody strongly suppressed MSC ability to migrate and generate capillary-like structures. Collectively, these data suggest that MSCs may have the capacity to participate in tumor angiogenesis through regulation of their angiogenic properties under an atmosphere of low oxygen that closely approximates the tumor microenvironment.