The Relation Between Sox9, TGF-��1, and Proteoglycan in Human Intervertebral Disc Cells

Objective

The aim of this study is to elucidate the effects of transforming growth factor-β (TGF-β)1 and L-ascorbic acid on proteoglycan synthesis, and the relationship between Sox9, proteoglycan, and TGF-β1 in intervertebral disc cells.

Methods

Human intervertebral disc tissue was sequentially digested to 0.2% pronase and 0.025% collagenase in DMEM/F-12 media and extracted cells were cultured in 37℃, 5% CO₂ incubator. When intervertebral disc cells were cultured with TGF-β1 or L-ascorbic acid, the production level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay. The changes of Sox9 mRNA and protein levels via TGF-β1 were detected by RT-PCR and Western blot analysis in each.

Results

The amount of sGAG was increased with the lapse of time during incubation, and sGAG content of pellet cultured cells was much larger than monolayer culture. When primary cultured intervertebral disc cells in monolayer and pellet cultures were treated by TGF-β1 20 ng, sGAG content of experimental group was increased significantly compared to control group in both cultures. L-Ascorbic acid of serial concentrations (50-300 ug/ml) increased sGAG content of mono layer cultured intervertebral disc cells significantly in statistics. The co-treatment of TGF-β1 and L-ascorbic acid increased more sGAG production than respective treatment. After treating with TGF-β1, Sox9 mRNA and protein expression rates were significantly increased in disc cells compared with the control group.

Conclusion

This study suggests that TGF-β1 would increase sulfated glycosaminoglycan (sGAG) and other proteoglycans such as versican by elevating Sox9 mRNA and protein expressions in order.     

The “Patient Presentation:” The Evolutions of a Practice,of Its Objectives,and of Its Effects on Training

ObjectivesThrough a review of the history of patient presentations and changes to this system, we will try to situate its function and challenges, particularly with regard to its effects on the training of professionals. The articulation of these effects with the necessary ethical questions raised by this practice will be highlighted.MethodThe review of the French-language literature on the practice of patient presentations makes it possible to note its permanence since the origins of psychiatry, its multiple challenges, the risks it has encountered over the course of its history, and the consequent changes that have resulted from it. A personal experience of patient presentations at the Centre Hospitalier Sainte-Anne over more than twenty years allows us to emphasize the essential elements of this exercise.ResultsPracticed mainly in recent years by psychoanalysts, the system of patient presentations has been considerably modified by taking into account the registers of language, speech, and the transference. The control or supervisory dimension also becomes a central function of this practice. This subversion makes it possible to significantly advance the controversies that run through its history. It also highlights its instructive effects, which, far from being limited to a pedagogical demonstration to inexperienced practitioners, involve practitioners in a place that allows them to question their position as well as their action, in their daily practice.DiscussionThe diversity of patient presentation systems, the variety of circumstances that led to their implementation in hospital services, the variable place they occupy in the organization of care, and the unequal interest that they can arouse on the part of healthcare teams justify identifying the essential benchmarks that make this practice so specific. The articulation of the three distinct places of the patient, the examiner, and the public – through the distinct knowledge attributed to each of these places – makes it possible to propose a reading of the structure of these presentations to examine their effects on the training of practitioners, as well as on clinical research.ConclusionIf clinical practice is developed and transmitted “at the patient's bedside” and in the dialogue between practitioners, then the presentation of the patient is one of the key places where clinical practice is developed. The ethical questions it raises thus constitute an opportunity for a renewal of the psychiatric clinic and its practice.     

The effects of aging and Alzheimer��s disease on associative recognition memory

We investigated the effects of aging and Alzheimer's disease (AD) on item and associative recognition memory. Three groups of participants (younger adults, elderly adults, and AD patients) studied photographs of common objects that were located on either the left or the right side of a black computer screen inside either a red or a blue square. In a subsequent old/new recognition memory test, the participants were presented with four kinds of stimuli: "intact" stimuli, which were presented as they were during the study phase; "location-altered" stimuli, which were presented in a different location; "color-altered" stimuli, which were presented with a different surrounding color; and "new" stimuli, which consisted of photographs that had not been presented during the study phase. Compared with younger adults, the older adults showed equivalent performance in simple item recognition but worse performance in discriminating location-altered and color-altered stimuli. Compared with older adults, the AD patients showed equivalent performance in discriminating color-altered stimuli but worse performance in simple item recognition and the discrimination of location-altered stimuli. We speculate that distinct structural and functional changes in specific brain regions that are caused by aging and AD are responsible for the different patterns of memory impairment.     

Why ��Willusionism�� Leads to ��Bad Results��: Comments on Baumeister, Crescioni, and Alquist

Drawing on results discussed in the target article by Baumeister et al. (1), I argue that the claim that the modern mind sciences are discovering that free will is an illusion (“willusionism”) is ambiguous and depends on how ordinary people understand free will. When interpreted in ways that the evidence does not justify, the willusionist claim can lead to ‘bad results.’ That is, telling people that free will is an illusion leads people to cheat more, help less, and behave more aggressively, but these responses may be based on people’s interpreting willusionist claims to mean that they lack the powers of rational choice and self-control.     

Health, Happiness and Human Enhancement—Dealing with Unexpected Effects of Deep Brain Stimulation

Deep Brain Stimulation (DBS) is a treatment involving the implantation of electrodes into the brain. Presently, it is used for neurological disorders like Parkinson’s disease, but indications are expanding to psychiatric disorders such as depression, addiction and Obsessive Compulsive Disorder (OCD). Theoretically, it may be possible to use DBS for the enhancement of various mental functions. This article discusses a case of an OCD patient who felt very happy with the DBS treatment, even though her symptoms were not reduced. First, it is explored if the argument that ‘doctors are not in the business of trading happiness’, as used by her psychiatrist to justify his discontinuation of the DBS treatment, holds. The relationship between enhancement and the goals of medicine is discussed and it is concluded that even though the goals of medicine do not set strict limits and may even include certain types of enhancement, there are some good reasons for limiting the kind of things doctors are required or allowed to do. Next, the case is discussed from the perspective of beneficence and autonomy. It is argued that making people feel good is not the same as enhancing their well-being and that it is unlikely—though not absolutely impossible—that the well-being of the happy OCD patient is really improved. Finally, some concerns regarding the autonomy of a request made under the influence of DBS treatment are considered.     

Good or Essential? The Effects of Victim Characteristics and Family Significance on Sentencing Judgments and Perceptions of Harm

Victim impact statements containing information about the character of the victim, as well as their significance to the family were varied across conditions to examine their effects on perceptions of harm and sentencing decisions for 166 death qualified participants. The results indicate that information concerning the victim's significance to their family significantly influenced sentencing judgments, whereas victim character information failed to do so. Perceptions of harm significantly mediated the relation between family significance and sentencing decisions. Implications for the Supreme Court ruling in Payne v. Tennessee (1991) and the relevance of including information about the victim as a means of communicating harm in capital trial sentencing are discussed.     

Effects of erythropoietin and its receptor on nervous system

INTRODUCTION Erythropoietin (EPO), as a kind of hemopoietic growth factors, is first- ly found by Bonsdor and Jalsvisto in 1948. It can promote the prolifer- ation and differentiation of erythroid cells and can promote the maturi- ty of erythroid progenit…     

Effects of Sex,Handedness, Stimulus and Visual Field on “Mental Rotation”

Shepard's mental rotation paradigm (e.g. Shepard and Metzler, 1971) was modified to allow tachistoscopic presentation of stimuli at varying angles of orientation (0° to 180°) in the right and left visual fields. Thirty male and thirty female subjects divided into three handedness groups (right-handers, non-familial and familial left-handers) judged whether a stimulus was a standard form or its mirror image. In general response times for correct judgements (RT_c) increased monotonically as a function of angle of orientation though the curves tended to be negatively accelerated rather than linear. Right-handers showed a slower rate of increase in RT_c as a function of angle than either left-handed group. Mean RT_c and the rate of increase in RT_c were equivalent for the two sexes and for the two visual fields. Both mean RT_cs and on the rate of increase in RT_c varied as a function of the stimulus.Error rates also increased monotonically as a function of angle of orientation. No sex or handedness differences in error rates were found. However, errors increased significantly less rapidly when stimuli were presented in the left visual field. It is argued that right hemisphere specialization for spatial processing minimizes the rate of increase in errors.The present failure to find sex differences may be of interest and it is argued that rapid presentation of stimuli results in subjects setting maximum and minimun response times. Within this relatively restricted “bandwith” of response times males and females may perform spatial tasks equally efficiently. Some confirmation for this hypothesis vs. an alternative based upon differences in hemispheric organization was found in a second experiment.     

Effects of acute and repeated administration of Staphylococcal enterotoxin A on Morris water maze learning, corticosterone and hippocampal IL-1β and TNFα

Staphylococcal enterotoxin A (SEA) is a bacterial superantigen that induces pronounced T cell expansion and cytokine production. In addition, SEA activates the HPA axis and forebrain regions relevant to cognitive functions. Since learning-related cognitive changes have not been assessed in response to SEA, spatial learning in the Morris water maze (MWM) was determined in male C57BL/6 J mice subjected to acute or repeated injections of 5 μg SEA or Saline. Injections were given 2 h prior to 4-5 days of hidden platform sessions. Animals were then rested for 1 month and given retraining without further injections. In addition, splenic IL-1β, IL-2 and TNFα, plasma corticosterone, and hippocampal IL-1β and TNFα were measured after the regimen of treatment used in the behavioral experiments. The results showed no learning impairment following acute or repeated SEA challenge. Moreover, when retested 1 month later, and without further injections, the SEA group showed more rapid relearning of the MWM. This suggested that coincidental superantigenic T cell activation and training served to promote long-term improvement in recovery of learning. Furthermore, repeated SEA challenge continued to drive increases in plasma corticosterone, but with a compensatory reduction in hippocampal IL-1β. However, while hippocampal TNFα was reduced after acute and repeated SEA treatment, this was not statistically significant. In view of the importance of modest glucocorticoid elevations and hippocampal IL-1β in promoting contextual learning, the data point to the hypothesis that SEA promotes long-term plasticity by restraining disruptive increases in hippocampal IL-1β, and possibly TNFα, during learning.     

The Effects of Fibrillar Forms of α-Synuclein Protein on Neurogenesis in the Hippocampus,Dopaminergic Neurons of the Substantia Nigra,and the Behavior of Ageing Mice

Hyperproduction and disturbance of the protein conformation of α-synuclein that are associated with the formation of aggregated forms, which have a neurotoxic effect, are the key link in the mechanisms of the pathogenesis of synucleinopathies, which are chronic progressive neurodegenerative diseases. We studied the effects of chronic intranasal administration of fibrillar forms of α-synuclein on the processes of neurogenesis in the hippocampus, the content of dopaminergic neurons in the substantia nigra, motor and exploratory activity, short- and long-term memory, and anxiety in ageing animals. The experiments were performed with 12-month-old male C57Bl/6 mice, which were administered intranasally once a day with a solution of α-synuclein fibrils or physiological solution for 14 days. Behavioral experiments included the Open field, novel object recognition, passive avoidance, and elevated plus maze tests. We used antibodies against bromodeoxyuridine, doublecortin, and tyrosine hydroxylase to stain proliferating cells, immature neurons, and dopaminergic nerve cells. We found that α-synuclein fibrils do not cause significant changes in indices of neurogenesis, the number of proliferating cells and immature neurons in the hippocampal dentate gyrus; nor do they have a significant effect on exploratory behavior, short- and long-term memory, and anxiety in mice. However, animals that were treated with fibrils of α-synuclein had a significant increase in the number of dopaminergic neurons in the substantia nigra pars compacta and an increase in some indices of general motor activity. We compared the data on the effects of α-synuclein fibrils and the results of a previous study of the action of α-synuclein oligomers under the conditions of a similar experimental protocol. We discuss possible mechanism of the revealed effect of α-synuclein fibrils on dopaminergic neurons of the substantia nigra of ageing mice.     

The Short-Term Effects of Risperidone-Induced Hyperprolactinemia on Lipid Metabolism in Drug-Na?ve Children and Adolescents

Objective

The present cross-sectional study was designed to assess the risk of elevated prolactin levels and other hormonal or metabolic changes in children and adolescents taking risperidone.

Methods

Twenty-five children and adolescents [aged 7-18 years, 12.1±3.3 years (mean±SD); 19 boys and 6 girls] who had been taking risperidone for at least 3 months were enrolled. The following blood parameters were measured: serum levels of prolactin, thyroid hormones, alanine transaminase (ALT), sex hormones, lipids.

Results

The median risperidone dosage was 1.55 mg/day (SD 1.14 mg/day, range 0.25-4.00 mg/day). The prolactin level (33.65±16.71 ng/mL, range 5.8-68.3 ng/mL) was higher than normal, and was elevated (≥15 ng/mL in male, ≥23.3 ng/mL in female) in about 84% of the patients. The dosage of risperidone was positively correlated with serum prolactin level (r=0.767, p<0.001). The TG/HDL ratio was higher in the group with higher prolactin levels (i.e., ≥30 ng/mL), and hence might be a useful marker of insulin resistance.

Conclusion

In young patients taking risperidone, a high serum prolactin level may influence lipid metabolism, even when cholesterol levels are within the normal range. Further investigation is needed around this issue. Serum prolactin assessment is recommended for children and adolescents taking risperidone.     

Impact of Calcium on Salivary ��-Amylase Activity, Starch Paste Apparent Viscosity, and Thickness Perception

Thickness perception of starch-thickened products during eating has been linked to starch viscosity and salivary amylase activity. Calcium is an essential cofactor for ??-amylase and there is anecdotal evidence that adding extra calcium affects amylase activity in processes like mashing of beer. The aims of this paper were to (1) investigate the role of salivary calcium on ??-amylase activity and (2) to measure the effect of calcium concentration on apparent viscosity and thickness perception when interacting with salivary ??-amylase in starch-based samples. ??-Amylase activity in saliva samples from 28 people was assessed using a typical starch pasting cycle (up to 95 °C). The activity of the enzyme (as measured by the change in starch apparent viscosity) was maintained by the presence of calcium, probably by protecting the enzyme from heat denaturation. Enhancement of ??-amylase activity by calcium at 37 °C was also observed although to a smaller extent. Sensory analysis showed a general trend of decreased thickness perception in the presence of calcium, but the result was only significant for one pair of samples, suggesting a limited impact of calcium enhanced enzyme activity on perceived thickness.     

Effects of aging and β-amyloid on the properties of brain synaptic and mitochondrial membranes

Summary. The effects of aging and of different amyloid β-peptides (Aβ) on the properties of purified synaptosomal plasma and mitochondrial membranes were studied using different fluorescent dyes. Aging led to opposite membrane alterations in both mouse brain fractions. Cholesterol levels were significantly enhanced in synaptosomal plasma membranes (SPM) from aged mice only. Flexibility of membrane fatty acids was decreased in synaptosomal plasma and mitochondrial membranes, mobility of pyrene was enhanced, but in SPM only. With regard to acyl chain flexibility in aged brain membranes, both membrane preparations were less sensitive to Aβ. By contrast, effects of Aβ on the mobility of pyrene were not reduced for aged synaptic membranes, but even seemed to be enhanced in the case of aged mitochondrial membranes. The data presented significantly enhance our understanding of the mechanism of the Aβ's disordering effects on synaptosomal membranes that are also detectable for mitochondrial membranes and show for the first time that Aβ effects are modified by brain aging. This is of special interest since membrane alterations and in particular modifications of membrane cholesterol were recently linked to Alzheimer's Disease. Received October 6, 2000; accepted April 2, 2001     

The effects of age on lipopolysaccharide-induced cognitive deficits and interleukin-1β expression

An acute LPS challenge immediately following day 1 of shuttlebox training triggered exacerbated central IL-1β production and disrupted memory consolidation and/or further acquisition of the task in 18-month-old mice, compared to 4-month-old controls. These deficits cannot be attributed to alterations in sickness behavior. The findings suggest that age and immune activation combine to impair learning and memory consolidation processes, and that increased central IL-1β production may play a role.     

Effects of pyridoxine and magnesium on autistic symptoms—Initial observations

In an open trial, a heterogeneous group of 44 children with autistic symptoms were treated with large doses of vitamin B₆ and magnesium. Clinical improvement with worsening on termination of the trial was observed in 15 children. Thirteen responders and 8 nonresponders were retested in a 2-week, crossover, double-blind trial, and the responses to the open trial were confirmed.This work was supported by CNRS (ERA 697) Biological Methods in Neuropsychiatry, INSERM ATP 78-97 and C.L.79, DGRST, DNP 78-7-2787, Fondation pour la Recherche Medicale and the Langley Porter Psychiatric Institute, University of California, San Francisco, California 94143. The pyridoxine was supplied by courtesy of Hoffman-LaRoche and Specia. We thank Ms. Gabard for her technical assistance, Ms. Besnardeau and Ms. Lioret for scoring the clinical data, and Danielle Thouvenin for editorial assistance.     

Differential Effects of Non-REM and REM Sleep on Memory Consolidation?

Sleep benefits memory consolidation. Previous theoretical accounts have proposed a differential role of slow-wave sleep (SWS), rapid-eye-movement (REM) sleep, and stage N2 sleep for different types of memories. For example the dual process hypothesis proposes that SWS is beneficial for declarative memories, whereas REM sleep is important for consolidation of non-declarative, procedural and emotional memories. In fact, numerous recent studies do provide further support for the crucial role of SWS (or non-REM sleep) in declarative memory consolidation. However, recent evidence for the benefit of REM sleep for non-declarative memories is rather scarce. In contrast, several recent studies have related consolidation of procedural memories (and some also emotional memories) to SWS (or non-REM sleep)-dependent consolidation processes. We will review this recent evidence, and propose future research questions to advance our understanding of the role of different sleep stages for memory consolidation.