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A novel follicle-cell-dependent dominant female sterile allele, StarKojak, alters receptor tyrosine kinase signaling in Drosophila.

We describe a new dominant allele, StarKojak, that alters receptor tyrosine kinase signaling in the follicle cells and in the eyes in Drosophila. We isolated StarKojak in a screen for follicle-cell-dependent dominant female sterile mutations. We show that StarKojak and revertants of StarKojak do not complement Star loss-of-function mutations. We propose that StarKojak is a novel type of allele of Star that has both dominant gain-of-function phenotypes early in development and dominant loss-of-function phenotypes later in development. Star encodes a putative transmembrane protein that has previously been shown to be a critical component of the epidermal growth factor receptor tyrosine kinase signaling pathway. Early in oogenesis, Star mRNA expression is higher in StarKojak egg chambers than in wild-type egg chambers, consistent with its gain-of-function phenotype. Later in oogenesis, Star mRNA expression is lower in StarKojak follicle cells than in wild-type follicle cells, consistent with its loss-of-function phenotype. By genetically analyzing StarKojak and its revertants, we present evidence that Star is involved in anterior-posterior axis formation both in the female germline cells and in the somatic follicle cells. We also demonstrate that at least part of the dominant female sterile phenotype of StarKojak is restricted to the posterior-pole follicle cells. We propose that Star functions by processing pro-Gurken to mature Gurken, which is thereby released in the region between the oocyte and the follicle cells and binds to the epidermal growth factor receptor in the follicle cells.

Alleles↗

A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data.

We conducted a two center, double-blind, placebo-controlled treatment trial with oral branched chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 8 g, and L-valine 6.4 g daily) or L-threonine (4 g daily) with pyridoxal phosphate (160 mg daily) for six months in patients with amyotrophic lateral sclerosis (ALS). The effect of treatment on disease progression was estimated every two months by recording clinical muscle strength, maximum isometric muscle torque in selected muscles, forced vital capacity (FVC), activities of daily living pertaining to the upper and lower limbs, and timed tasks. Ninety-five patients were randomized to receive BCAA (n = 31), L-threonine (n = 32), or placebo (n = 32), of whom 77 (81%) completed the trial. Mean weight loss in the placebo group was 1.1 kg and in the L-threonine group was 3.2 kg; the BCAA group gained 0.2 kg (p = 0.04). The estimated decline in FVC was about 2.5 times greater in the BCAA and L-threonine groups as compared to placebo (p = 0.03). Otherwise, no significant differences were found in the changes observed in clinical, functional, timed, or maximum torque measures among treatment groups. The amino acids were well tolerated. The results of our study failed to show a beneficial effect of BCAA or L-threonine treatment for six months on the disease course in ALS. The higher rate of loss of pulmonary function in patients treated with BCAA or L-threonine may have been due to chance, but an adverse effect of these amino acids cannot be ruled out.

Adult↗

Field dependence, laterality and the EEG.

There is evidence that an individual's 'cognitive style' is related to lateralization of function in the brain, and that this in turn is associated with characteristic EEG coherence spectra. We tested the hypothesis that field dependence (a measure of cognitive organization) and hand preference (a measure of functional organisation) relate to EEG coherence measures in a specific way. The predicted associations were based on the proposal that right preferent individuals have a more specific, and left preferents a more diffuse, system of functional units in the cortex. The association between alpha band resting EEG coherence (sampled on two occasions for both hemispheres from 12 right and 12 left preferent individuals), field dependence (Nyborg's criterion of frame dependence on a rod and frame test), and laterality scores (questionnaire and manual performance), was measured by Kendall's coefficient of concordance (W). Significant associations support the proposed model except for coherence within the left preferents' right hemisphere. It is argued that the right hemisphere is more specifically organised in strong sinistrals than the general model would predict. These and other results support the use of EEC coherence measures in the study of cerebral functional organisation.

Adult↗

A dissociation of dorso-lateral striatum and amygdala function on the same stimulus-response habit task.

This experiment tested the idea that the amygdala-based learning and memory system covertly acquires a stimulus-reward (stimulus-outcome) association during acquisition of a stimulus-response (S-R) habit task developed for the eight-arm radial maze. Groups of rats were given dorso-lateral striatal or amygdala lesions and then trained on the S-R habit task on the eight-arm radial maze. Rats with neurotoxic damage to the dorso-lateral striatum were severely impaired on the acquisition of the S-R habit task but showed a conditioned-cue preference for the stimulus reinforced during S-R habit training. Rats with neurotoxic damage to the amygdala were able to acquire the S-R habit task but did not show a conditioned-cue preference for the stimulus reinforced during S-R habit training. This pattern of results represents a dissociation of learning and memory functions of the dorsal striatum and amygdala on the same task.

Amygdala↗

The frenectomy combined with a laterally positioned pedicle graft. Functional and esthetic considerations.

In many cases it is necessary to perform a frenectomy to prevent reopening of a midline diastema following closure by orthodontic therapy. Often the loss of the interdental papilla between the maxillary incisors during the classic frenectomy creates an unacceptable esthetic result. A surgical technique combining a frenectomy with a laterally positioned pedicle graft is presented. The interdental papilla is left surgically undisturbed if it is of physiologic size. If it is enlarged, gingivoplasty is performed to reduce it to an appropriate size. Closure across the midline by laterally positioning gingiva and healing by primary intention results in attached gingiva across the midline. This attached gingiva may have a bracing effect and thus aid in preventing orthodontic relapse (reopening of the diastema). Twenty-seven cases were treated. No relapse was found in 24 cases and in 3 cases only minimal relapse was noted (less than 1 mm). The esthetic result is superior to that obtained with the classic frenectomy technique.

Esthetics, Dental↗

Lateral inhibition in the olfactory bulb and in olfaction.

Lateral inhibition in the olfactory bulb is mediated by circuits that involve reciprocal dendrodendritic connections between mitral and granule cells. Because of the properties of these connections and also because odor stimuli are not represented in an obviously topographic fashion, questions have been raised about whether the function of local inhibition in the olfactory bulb can be compared to the function of inhibition in other brain areas. Here, I propose an analysis of local inhibition in the olfactory bulb based on the simplification that olfactory bulb circuitry can be thought of as implementing a simple linear two-dimensional filter. This analysis highlights some important characteristics of the circuitry of the olfactory bulb and suggests that the function of lateral inhibition in the olfactory bulb may be to compensate for generalized, spatially distributed activation that otherwise may obscure the specific, discrete patterns of glomerular activation seen across the olfactory bulb.

Animals↗

Constitutive hyperdopaminergia is functionally associated with reduced behavioral lateralization.

According to the dopamine (DA) hypothesis of schizophrenia and the strong evidence for decreased cerebral lateralization in schizophrenic patients, we postulated that hyperactivity of the dopaminergic system could be associated with a reduced behavioral lateralization in mice. Mice lacking the dopamine transporter (DAT) gene were used as a genetic model of persistent hyperdopaminergia. The DAT null mutation was transferred on C57BL/6JOrl (B6) and DBA/2JOrl (D2) inbred backgrounds for more than 10 generations of backcrossing to derive three DAT strains, B6, D2, and B6xD2(F1). Adult mutant mice of the three DAT strains and their littermates were tested for paw preference using Collins' protocol. Our results demonstrated that, whatever the genetic background, persistent hyperdopaminergia directly impairs the degree of lateralization without affecting the direction. Our results support the degree of lateralization as a good candidate phenotype to further improve genetic analysis of cerebral lateralization in normal and pathological conditions.

Animals↗

[The functional asymmetry of the rabbit lateral hypothalamus during food motivation].

Thresholds and stability of food motivational reactions induced by electrostimulation of the left and right hypothalamus were studied in rabbits. Food reactions evoked by stimulation of the left hypothalamus had the lower thresholds and higher stability than those evoked by the stimulation of symmetrical areas. The asymmetry of the lateral hypothalamus in food reactions was not correlated with motor and sensory asymmetric.

Animals↗

Vagal tone and the physiological regulation of emotion.

On the basis of current knowledge of neuroanatomy and our previous research with cardiac vagal tone, we have proposed the vagal circuit of emotion regulation. The vagal circuit of emotion regulation incorporates lateral brain function with the regulation of the peripheral autonomic nervous system in the expression of emotion. The vagus and the vagal circuit do not function independently of other neurophysiological and neuroendocrine systems. Research on brain activity (see Dawson, in this volume; Fox, in this volume) and research on adrenocortical activity (see Stansbury & Gunnar, in this volume) demonstrate that EEG and cortisol are related to emotion states and to individual differences similar to those that we have investigated. The vagal circuit emphasizes not only the vagus but also the lateralization of specific brain structures in emotion regulation. The emphasis of the vagal circuit on right-brain-stem structures stimulates several testable hypotheses regarding the function of specific structures in the right brain in emotion regulation. These speculations are consistent with other reports (see Dawson, in this volume; Fox, in this volume) describing asymmetrical EEG activity during expressed emotions. Moreover, the vagal circuit does not exist independently of the brain structures and peptide systems regulating cortisol (see Stansbury & Gunnar, in this volume). Areas in the brain stem regulating vagal activity are also sensitive to the peptides that regulate cortisol (e.g., vasopressin and corticotropin-releasing hormone). In this essay, we have provided information regarding the relation between vagal tone and emotion regulation. A review of research indicates that baseline levels of cardiac vagal tone and vagal tone reactivity abilities are associated with behavioral measures of reactivity, the expression of emotion, and self-regulation skills. Thus, we propose that cardiac vagal tone can serve as an index of emotion regulation. Historically, the vagus and other components of the parasympathetic nervous system have not been incorporated in theories of emotion. Recent developments in methodology have enabled us to define and accurately quantify cardiac vagal tone. Theories relating the parasympathetic nervous system to the expression and regulation of emotion are now being tested in several laboratories.

Affect↗

Pseudoneglect of males and females on a spatial short-term memory task.

The effect of sex on the phenomenon of pseudoneglect was assessed in 60 male and 61 female right-handed subjects using a modified form of Corsi's block-tapping test. A significant right-lateralized pseudoneglect for both sexes was found, and the level of pseudoneglect strongly correlated with neglect in the right hemispace. Men were significantly more accurate in the left hemispace than women, whereas no difference was seen between the sexes in the right hemispace. Although we found some indirect evidence from which to infer that the men's brain may be functionally more lateralized than the women's for this spatial task, there was no significant difference between the sexes in correct responses for the left hemispace, i.e., right pseudoneglect. Therefore, the results suggest that pseudoneglect phenomenon can be partly explained by a functional asymmetric feature of the brain, and the other factors probably play a role in producing the similar patterns of asymmetric perception of space in males and females.

Adult↗

Serial changes in pulmonary functions in children hospitalized with cystic fibrosis.

Pulmonary functions were serially measured in 17 children hospitalized with cystic fibrosis (CF) to determine how much and when pulmonary functions improved during 14 days of inpatient treatment. Absolute lung volumes and forced expiratory flows were recorded every other day while patients received chest physiotherapy, antibiotics, and bronchodilators. Vital capacity first improved after the fifth hospital day coincidentally with a reduction in residual volume and an increase in peak expiratory flow rate. Significant improvements in other pulmonary functions developed later in the hospitalization. Improvement in most pulmonary functions continued throughout the hospitalization and was maintained 2 wk after discharge. Improvement was less and uniformly developed later in those children with severe lung disease on admission (NIH score less than 50) compared with those with moderate respiratory involvement (NIH score greater than 50). Pulmonary function measurements may prove useful in determining the optimal duration of treatment for patients who are hospitalized with CF.

Adolescent↗

The effect of lateral and dorsal recumbency on cardiopulmonary function in the anaesthetised horse.

The effect of lateral and dorsal recumbency on cardiopulmonary function in six anaesthetised horses were compared. Cardiac output/kg, stroke volume/kg, alveolar ventilation, venous admixture, pulmonary shunt and blood-gas values were determined. From lateral to dorsal recumbency cardiac output/kg decreased non-significantly. A significant increase in pulmonary shunt occurred. A positive correlation between body mass and pulmonary shunt in dorsal recumbency was found. Alveolar ventilation increased significantly in dorsal recumbency when breathing air compared to oxygen.

Anesthesia, Intravenous↗

The hippocampus, space, and viewpoints in episodic memory.

A computational model of how single neurons in and around the rat hippocampus support spatial navigation is reviewed. The extension of this model, to include the retrieval from human long-term memory of spatial scenes and the spatial context of events is discussed. The model explores the link between spatial and mnemonic functions by supposing that retrieval of spatial information from long-term storage requires the imposition of a particular viewpoint. It is consistent with data relating to representational hemispatial neglect and the involvement of the mammillary bodies, anterior thalamus, and hippocampal formation in supporting both episodic recall and the representation of head direction. Some recent behavioural, neuropsychological, and functional neuroimaging experiments are reviewed, in which virtual reality is used to allow controlled study of navigation and memory for events set within a rich large-scale spatial context. These studies provide convergent evidence that the human hippocampus is involved in both tasks, with some lateralization of function (navigation on the right and episodic memory on the left). A further experiment indicates hippocampal involvement in retrieval of spatial information from a shifted viewpoint. I speculate that the hippocampal role in episodic recollection relates to its ability to represent a viewpoint moving within a spatial framework.

Animals↗

Beyond speech lateralization: a review of the variability, reliability, and validity of the intracarotid amobarbital procedure and its nonlanguage uses in epilepsy surgery candidates.

While the intracarotid amobarbital procedure (IAP) was originally utilized to lateralize speech functions as an aid in the surgical treatment of epilepsy, additional uses for the IAP have emerged including: (1) the use of the IAP to predict post-surgical memory changes, including both global amnesia and smaller, yet significant, material-specific memory deficits; (2) the use of the IAP to provide confirmatory evidence of lateralization of seizure focus; and (3) the use of the IAP to predict post-surgical relief from seizures. While the literature on the IAP is extensive and growing, its utility is marred by the wide variability associated with the procedure itself from epilepsy center to center. This variability renders comparisons among IAP studies problematic and conclusions about IAP efficacy difficult. The variability associated with the amobarbital procedures, as well as the reliability and the validity of the IAP in its nonlanguage uses is reviewed here. A special emphasis is devoted to research conducted in the last decade. Also discussed is the future of the IAP including anticipated research directions.

Amobarbital↗

Surgical management of velopharyngeal incompetence in velocardiofacial syndrome.

OBJECTIVES: To analyze the results of surgery for velopharyngeal incompetence (VPI) in velocardiofacial syndrome. DESIGN: Prospective data collection, with randomized, blind assessment of speech and velopharyngeal function on lateral videofluoroscopy and nasendoscopy. SETTING: Two-site, tertiary referral cleft unit. PATIENTS: Forty-two consecutive patients with the 22q11 deletion underwent surgery for symptomatic VPI by a single surgeon. INTERVENTIONS: Intraoral examinations, lateral videofluoroscopy (+/- nasendoscopy) and intraoperative evaluation of the position of the velar muscles through the operating microscope. Based on these findings, either a radical dissection and retropositioning of the velar muscles (submucous cleft palate [SMCP repair]) or a Hynes pharyngoplasty (posterior pharyngeal wall augmentation pharyngoplasty) was performed. As anticipated, a proportion of patients undergoing SMCP repair subsequently required a Hynes. The aim of this staged approach was to maximize velar function, thereby enabling a less obstructive pharyngoplasty to be performed. Thus, there were three surgical groups for analysis: SMCP alone, Hynes alone, and SMCP+Hynes. MAIN OUTCOME MEASURES: Blind perceptual rating of resonance and nasal airflow; blind assessment of velopharyngeal function on lateral videofluoroscopy and nasendoscopy; and identification of predictive factors. RESULTS: Significant improvement in hypernasality in all three groups. The SMCP+Hynes group also showed significant improvement in nasal emission. There were significant improvements in the extended and resting velar lengths following SMCP repair and a trend toward increased velocity of closure. CONCLUSIONS: Depending on velopharyngeal anatomy and function, there is a role for SMCP repair, Hynes pharyngoplasty, and a staged combination of SMCP+Hynes, all of which are procedures with a low morbidity.

Adolescent↗

Material-specific memory in the intracarotid amobarbital procedure.

We examined material-specific memory in 45 left hemisphere language dominant patients with temporal complex partial seizures (24 right, 21 left) during the intracarotid amobarbital procedure (IAP) by showing eight cards displaying two line drawings of common objects, two printed words, one colored shape, one math expression, one face, and one abstract shape following amobarbital injection (mean = 109.9 mg). We assessed delayed recall and recognition following clearing. Patients with right foci recognized significantly fewer verbally mediated stimuli (words, object drawings, colored shape) with left than with right injection. Patients with left foci recognized a nonverbal stimulus (abstract shape) more poorly following right versus left injection. Discriminant function analysis lateralized 85% of the sample from memory predictors, upheld to 81% on crossvalidation. Material-specific memory remains intact in the hemisphere contralateral to a seizure focus, but wider representation may occur for stimuli normally dominant for the hemisphere with the seizure focus. The IAP significantly lateralizes a seizure focus with use of both types of stimuli.

Amobarbital↗

The lateral superior olive: a functional role in sound source localization.

Sound location in azimuth is signaled by differences in the times of arrival (interaural time difference, ITDs) and the amplitudes (interaural level differences, ILDs) of the stimuli at the ears. Psychophysical studies have shown that low- and high-frequency sounds are localized based on ITDs and ILDs, respectively, suggesting that dual mechanisms mediate localization. The anatomical and physiological bases for this "duplex theory" of localization are found in the medial (MSO) and lateral (LSO) superior olives, two of the most peripheral sites in the ascending auditory pathway receiving inputs from both ears. The MSO and LSO are believed to be responsible for the initial encoding of ITDs and ILDs, respectively. Here the author focuses on ILDs as a cue to location and the role of the LSO in encoding ILDs. Evidence from disparate fields of study supports the hypothesis that the LSO is the initial ILD processor in the mammalian auditory system.

Animals↗

Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion.

BACKGROUND: Edaravone has potent free radical quenching and antioxidant actions. The agent has been recently in commercial use for acute ischemic stroke patients. In this study, we investigated the therapeutic effect of edaravone on severe carotid-territorial stroke. METHODS: Stroke patients with internal carotid artery occlusion and baseline NIH Stroke Scale Score > or =15 were treated for 14 days with drip intravenous infusion of edaravone (n=30) and were compared with a historical control cohort of similar patients (n=31). Glycerol was also administered to all patients in both groups. RESULTS: Infarct volume (P<0.02) and midline shift (P<0.02) on CT performed on day 2 of the patients treated with edaravone were smaller than those without edaravone. For patients with edaravone, infarct volume (P<0.0001) and midline shift (P<0.0001) on days 5-7 were greater than those on day 2. Hemorrhagic transformation of infarcts on day 2 was less severe in patients with than without edaravone (P<0.03). Within 14 days after the onset of stroke, 6 patients with edaravone (20%) and 14 without edaravone (45%) died directly of stroke (P<0.03). Among all patients, only two treated with edaravone were independent without any assistance 8 weeks after the onset. CONCLUSIONS: Edaravone was associated with delayed evolution of infarcts and edema in patients with severe carotid-territorial stroke and decreased mortality during the acute stage. The agent, however, failed to prevent evolution of infarcts and edema on later days, and did not significantly improve functional outcome among the surviving patients.

Aged↗