Adherence of botulinum and tetanus neurotoxins to synaptosomal proteins

The ability of 125I-labeled botulinum type A and tetanus neurotoxins to adhere to blots of synaptosomal proteins separated by SDS-polyacrylamide gel electrophoresis was studied. Both neurotoxins appeared to adhere preferentially to an approximately 80 kDa and to a lesser extent to an approximately 116 kDa protein(s). Adherence of the neurotoxins to these proteins was enhanced by preincubation of the neurotoxins with GT 1b. The approximately 100 kDa heavy chain segment of BTxA adhered to the same proteins. The carboxy terminal half of the heavy chain adhered primarily to the approximately 80 kDa protein(s) while the amino terminal portion bound most intensely to the approximately 116 kDa protein(s). The ability of the approximately 80 and approximately 116 kDa proteins to stain positively with the periodic acid-Schiff reagent and to bind 125I-labeled wheat germ lectin suggests that they are glycosylated. Both neurotoxins appear to adhere to the same approximately 80 and approximately 116 kDa proteins because tetanus neurotoxin preincubated with GT 1b was able to reduce binding of radiolabeled botulinum type A neurotoxin to both proteins. Neither neurotoxin adhered to blots of proteins from liver, spleen, or kidney, suggesting that the proteins adhered to are neural components.     

Electrical stimulation of the substantia nigra does not increase tail-flick latency in the rat

The effect of electrical stimulation at multiple sites in the midbrain was investigated in rats lightly anesthetized with barbiturate. The application of monopolar electrical stimulation to the substantia nigra (SN) or the adjacent cerebral peduncle failed to produce an elevation in tail-flick latency (TFL) in response to the application of noxious radiant heat. However, the same intensity of stimulation when applied to an area dorsal to the SN led to an elevation in TFL. This effect was not due to current spread to dopaminergic neurons in the zona compacta compartment of the SN because administration of cis-flupenthixol failed to block the effect. We conclude that, contrary to previous suggestions, discrete electrical stimulation of the SN itself does not give rise to a state of antinociception.     

Science and the future of psychiatry

If humanity is lucky, the evolution of our knowledge of the living world will result in the elaboration of more perfect scientific eyes to probe the nature of the human brain and to understand the complexities of the human mind. This seems to be the best path to truly helping individuals who are battling psychiatric illnesses and to actually preventing many brain-related disorders. For such accomplishments to take place, the trajectory of our science has to change, to move from its unrelenting reductionism to a serious attempt at integrating knowledge that spans from the structure of the gene to the expression of complex cognition. The tension between the biomedical and the psychotherapeutic approaches in psychiatry needs to be eliminated and transformed into a fully integrated approach that is mindful of the biological, emotional, cognitive, and social complexity of each individual.     

轻度认知障碍^18F-FDG PET显像的研究进展

轻度认知障碍(MCI)的病理改变与早期或临床前期阿尔茨海默病(AD)相似,MCI患者已经成为预测AD是否发生、有效延缓或早期干预治疗AD的最适群体,FDG PET脑功能显像可反映局部脑内葡萄糖代谢率,为MCI的病理学研究及临床诊断提供一种新的可靠工具.正确认识MCI与正常脑老化、AD脑葡萄糖代谢的不同、FDG PET图像特征及影响因素、对于预测病程及早期干预治疗、检测治疗效果、预防AD的发生及提高老年人生活质量有着重要的意义.     

Ascending projections to the mammillary nuclei in the rat: a study using retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase

Cells of origin of ascending afferents to the mammillary nuclei and the afferents' fields of termination within these nuclei were studied by using retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase in the rat. The pars compacta of the superior central nucleus projects bilaterally to the median region of the medial mammillary nucleus. The ventral tegmental nucleus projects ipsilaterally to the medial mammillary nucleus, except for its median region, in a topographic manner such that the rostrodorsolateral part of the ventral tegmental nucleus projects to the medial quadrant of the medial mammillary nucleus; the rostroventromedial part projects to the dorsal quadrant; the caudodorsolateral part projects to the ventral quadrant; and the caudoventromedial part projects to the lateral quadrant. These projection fields extend throughout the longitudinal axis of the medial mammillary nucleus, except for its most caudal region, to which only the dorsolateral part of the ventral tegmental nucleus projects. This nucleus also projects topographically to the ipsilateral dorsal premammillary nucleus; the rostral part of the ventral tegmental nucleus projects to the dorsal part of the dorsal premammillary nucleus, whereas the caudal part projects to the ventral part. The periaqueductal gray around the dorsal tegmental nucleus projects bilaterally to the supramammillary nucleus. The pars alpha of the pontine periaqueductal gray projects bilaterally to the peripheral part of the lateral mammillary nucleus, whereas the pars ventralis of the dorsal tegmental nucleus projects ipsilaterally to the lateral mammillary nucleus. The results show that the tegmentomammillary projections are organized in a gradient fashion, with the rostral to caudal position of cells of origin within the tegmental nuclei of Gudden being reflected by the medial to lateral position of fields of termination within the mammillary nuclei.     

Are universities preparing nurses to meet the challenges posed by the Australian mental health care system?

The preparedness of comprehensive nurses to work with the mentally ill is of concern to many mental health professionals. Discussion as to whether current undergraduate nursing programs in Australia prepare a graduate to work as a beginning practitioner in the mental health area has been the centre of debate for most of the 1990s. This, along with the apparent lack of interest and motivation of these nurses to work in the mental health area following graduation, remains a major problem for mental health care providers. With one in five Australians now experiencing the burden of a major mental illness, the preparation of a nurse who is competent to work with the mentally ill would appear to be a priority. The purpose of the present study was to determine third year undergraduate nursing students' perceived level of preparedness to work with mentally ill clients. The results suggested significant differences in students' perceived level of confidence, knowledge and skills prior to and following theoretical and clinical exposure to the mental health area. Pre-testing of students before entering their third year indicated that the philosophy of comprehensive nursing: integration, although aspired to in principle, does not appear to occur in reality.     

Bayesian adaptive non-inferiority with safety assessment: retrospective case study to highlight potential benefits and limitations of the approach

Adaptive trial design applied to randomized clinical trials of psychiatric medicines offers the potential to make clinical trials more efficient. In the current analysis, we retrospectively applied Bayesian adaptive allocation methods to a case study in agitated patients with schizophrenia and related diseases. The original study used a randomized, double-blind, parallel design. The objective of this analysis was to demonstrate the potential benefits of Bayesian adaptive designs by shortening the study duration and therefore limiting patient exposure to ineffective placebo or an active comparator with a known side effect. Bayesian methods allowed us to fully leverage historical data along with data observed as the study was ongoing to calculate predictive probabilities of patient response to treatment without experiencing a specified side effect. Using the Bayesian adaptive approach would have required less than half the number of patients as the original study to draw the same conclusion. Sample size was reduced from 311 to 156 patients, thereby decreasing the number of patients exposed to placebo from 54 to 30 and the number exposed to the active control with a known side effect from 126 to 60.     

Efferent projections of the basolateral amygdala in the opossum, Didelphis virginiana

The autoradiographic anterograde axonal transport technique was used to study efferent projections of the opossum basolateral amygdala. All nuclei of the basolateral amygdala send topographically organized fibers to the bed nucleus of the stria terminalis (BST) via the stria terminalis (ST). Injections into rostrolateral portions of the basal nuclei label fibers that surround the commissural bundle of the ST, cross the midline by passing along the outer aspect of the anterior commissure, and terminate primarily in the contralateral BST, anterior subdivision of the basolateral nucleus (BLa), ventral putamen, and olfactory cortex. Each of the basal nuclei project ipsilaterally to the anterior amygdaloid area, substantia innominata and topographically to the ventral part of the striatum and adjacent olfactory tubercle. The posterior subdivision of the basolateral nucleus (BLp), but not the basomedial nucleus (BM), projects to the ventromedial hypothalamic nucleus. BLa and BLp have projections to the nucleus of the lateral olfactory tract and also send fibers to the central nucleus, as does the lateral nucleus (L). The lateral nucleus also has a strong projection to BM and both nuclei project to the amygdalo-hippocampal area. BLa and BLp send axons to the ventral subiculum and ventral lateral entorhinal area whereas L projects only to the latter area. The lateral nucleus and BLp project to the perirhinal cortex and the posterior agranular insular area. The BLa sends efferents to the anterior agranular insular area. Rostrally this projection is continuous with a projection to the entire frontal cortex located rostral and medial to the orbital sulcus. All of the nuclei of the basolateral amygdala project to areas on the medial wall of the frontal lobe that appear to correspond to the prelimbic and infralimbic areas of other mammals. Despite the great phylogenetic distance separating the opossum from placental mammals, the projections of the opossum basolateral amygdala are very similar to those seen in other mammals. The unique frontal projections of the opossum BLa to the dorsolateral prefrontal cortex appear to be related to the distinctive organization of the mediodorsal thalamic nucleus and prefrontal cortex in this species.     

High utilizers of psychiatric emergency services

OBJECTIVE: The purpose of this study was to examine the sociodemographic and clinical characteristics of high utilizers of psychiatric emergency services. METHODS: Data were collected over four years for 761 patients who were identified as high utilizers according to three definitions (two standard deviations above the mean number of visits to an urban psychiatric emergency service, six visits in a year, and four visits in a quarter) and for 1,585 nonfrequent utilizers (control group). Univariate analysis of variance and logistic regression models were used to determine group differences. RESULTS: Two distinct groups of high utilizers emerged: high utilizers by quarter and high utilizers by standard deviation. Compared with the control group, the high utilizers were more likely to be homeless, to have developmental delays, to be enrolled in a mental health plan, to have a history of voluntary and involuntary hospitalizations, to be uncooperative, to have personality disorders, to have unreliable social support, and to have a lifetime history of incarceration and detoxification. Compared with the high utilizers by quarter, the high utilizers by standard deviation had more visits and were more likely to have a history of incarceration and psychiatric hospitalization, more likely to be enrolled in mental health plan, and less likely to be homeless. CONCLUSIONS: High utilizers make up a small percentage of individuals who seek care in psychiatric emergency services and disproportionately use resources. It may be helpful to use two definitions of high utilizer to identify patients at different phases of their illness and to guide clinical interventions and mental health policies.     

On a symptom which corresponds with "schizophrenic color" as the impression of schizophrenic disturbance of rapport

It is suggested that "schizophrenic color", as the impression of schizophrenic disturbance of rapport, is closely related to the disturbance of communication, especially metacommunication, by many researchers. So the author defined a symptom named "the cognitive schema of others' position", which means others' time-space position in a patient's delusional world, as the symptom being expected to be closely related to the disturbance of the patient's metacommunication at the interaction with others in his delusional world. Then the author examined statistically the relationship of "schizophrenic color" (or the operational diagnosis of schizophrenia according to DSM-III) to "the cognitive schema of others' position" and at the same time to several forms of auditory hallucination having been considered to be significantly related to schizophrenia. 58 hallucinatory-delusional states (29 schizophrenia, 29 non-schizophrenia) were actually examined and some results were pointed out as follows. Observation of the "improper cognitive schema of others' position", which means the fantastic and impossible, for a human being, time-space position of others in a patient's delusional world, was statistically related to the deterioration of "schizophrenic color" or the operational diagnosis of schizophrenia according to DSM-III. This result was considered to be related to the supposition that the "improper cognitive schema of others' position" is a symptom representing the schizophrenic collapse of the cognitive time-space construction as well as the schizophrenic disturbance of metacommunication. Otherwise, the observation of hallucinatory voices speaking and answering directly to the patient, which has been expected to be one of the most important symptoms of schizophrenia, was not statistically related to the deterioration of "schizophrenic color" or the operational diagnosis of schizophrenia according to DSM-III. And the observation of hallucinatory voices arguing about the patient in the third person was statistically related to the improvement of "schizophrenic color" or the operational diagnosis of the non-schizophrenic hallucinatory-delusional state according to DSM-III. Both statistical relationship above were considered to be explained generally from the relationship of "the cognitive schema of others' position" to schizophrenia. According to these results it was finally concluded that the "improper cognitive schema of others' position" is one of the most significant symptoms of the schizophrenic situation represented by the deterioration of "schizophrenic color" or the operational diagnosis of schizophrenia according to DSM-III.     

The Neuroscience of Decision Making and Our Standards for Assessing Competence to Consent

Rapid advances in neuroscience may enable us to identify the neural correlates of ordinary decision making. Such knowledge opens up the possibility of acquiring highly accurate information about people’s competence to consent to medical procedures and to participate in medical research. Currently we are unable to determine competence to consent with accuracy and we make a number of unrealistic practical assumptions to deal with our ignorance. Here I argue that if we are able to detect competence to consent and if we are able to develop a reliable neural test of competence to consent, then these assumptions will have to be rejected. I also consider and reject three lines of argument that might be developed by a defender of the status quo in order to protect our current practices regarding judgments of competence in the face of the availability of information about the neural correlates of ordinary human decision making.     

Spécificités de la psycho-oncologie du sujet âgé

The specificity of cancer is at the origin of emotional, cognitive and behavioural reactions in old age as well as in other stages of life. It is important to understand the particularities due to ageing to be able to listen to, to help express emotions, to inform and to better support patients. That is why in this paper the authors envisage the psychological vulnerability of elderly persons, the psychological processes at work from the first symptom of cancer to the treatment phase via investigations and announcing the diagnosis. Finally they evoke the psychopathological disorders that arise with elderly patients with cancer and the specificities of the diagnosis approach.     

Dynamic-static sensitivity of rat chorda tympani fibers to anodal current applied to the tongue

Responses of rat single chorda tympani fibers to anodal current of varying rise rates and current intensities applied to the tongue were examined. Thirteen out of fifteen chorda tympani fibers were sensitive to both rate of current rise and current intensity. However, sensitivities to these two stimulus parameters were different among 13 fibers. The remaining two fibers were not sensitive to the rate of current rise, but sensitive to current intensity. It was suggested that sensitivity to the rate of current rise was independent from that to current intensity.     

Neural membrane glycoproteins associated with chicken Thy-1: an anti-idiotypic antibody study

In order to investigate the possible binding of Thy-1 to other neuronal cell surface proteins, anti-idiotypic antibodies were raised using a panel of anti-Thy-1 monoclonal antibodies. Anti-idiotypic antibodies were selected for their ability to bind to day-old chick brain membrane components in enzyme-linked immunosorbent assays (ELISA), and to bind to membrane glycoproteins as determined by Western transfer immunoblotting assays. The 5 monoclonal anti-idiotypic antibodies bind to a membrane glycoprotein component of 70 kDa, and one of the antibodies also binds to 3 higher molecular weight components of 160 kDa, 120 kDa and 90 kDa. These antibodies bind to areas of the chicken cerebellum known to be rich in Thy-1. It is postulated that these molecules are associated with Thy-1, and that the role of Thy-1 on the neuronal cell surface, may be to form complexes with, and/or to stabilise these higher molecular weight glycoproteins during synaptic development.     

Differences in word associations to pictures and words

Normal subjects were asked to produce the "first word that comes to mind" in response to pictures or words that differed with respect to manipulability and animacy. In separate analyses across subjects and items, normal subjects produced a significantly higher proportion of action words (that is, verbs) to pictures as compared to words, to manipulable as compared to non-manipulable stimuli and to inanimate as compared to animate stimuli. The largest proportion of action words was elicited by pictures of non-living, manipulable objects. Furthermore, associates to words matched standard word associates significantly more often than those elicited by pictures. These data suggest that pictures and words initially contact different forms of conceptual information and are consistent with an account of semantic organization that assumes that information is distributed across different domains reflecting the mode of acquisition of that knowledge.     

Risk factors associated with children lost to care in a state early childhood intervention program

A retrospective cohort study was conducted to identify risk factors associated with children lost to care, and their families, compared to those not lost to care within the California Early Start Program. The cohort included data on 8987 children enrolled in the Early Start Program in 1998. This cohort consisted of 2443 children lost to care, 6363 children not lost to care, and 187 children that were lost to follow-up due to death or moving outside the state of California. Premature birth was the only medical risk factor in this study related to an increased risk of loss. Family risk factors exert a significant effect on loss to care. Risk factors that are predictive of loss to care include mother's age and educational level, Medi-Cal ineligibility, and lack of transportation. By identifying and examining risk factors for loss to care, interventions may be strengthened to promote continued family participation in early intervention services.     

Effects on the postnatal development of the mouse of preconception, postconception and/or suckling exposure to manganese via maternal inhalation exposure to MnO2 dust

Female mice were exposed either to MnO2 dust (7 hours/day, 5 days/week) or filtered air (control group) for 16 weeks prior to conception. On day 1 of gestation, half of each of these groups was assigned randomly either to MnO2 dust or filtered air exposure until day 17 of gestation. To separate effects of prenatal maternal exposure to MnO2 from postnatal exposure of offspring to Mn via suckling, a complete fostering/-cross-fostering design was employed. Compared to control mothers, mothers exposed to MnO2 prior to conception produced significantly larger litters. Prenatal exposure resulted in reduced neonatal activity scores and retarded offspring growth that persisted into adulthood. Offspring reared by mothers exposed to MnO2 prior to conception and filtered air postconception had significantly lower day 7 postpartum weights compared to offspring reared by mothers exposed to filtered air both prior to and postconception. Also, offspring reared by mothers exposed to MnO2 prior to conception and filtered air postconception had higher day 12 activity scores compared to offspring reared by mothers exposed to filtered air prior to conception and MnO2 postconception. Prenatal exposure to MnO2 depressed neonate activity and continued exposure, via suckling, intensified this depression. Offspring exposed prenatally to MnO2 were retrieved faster than control offspring. Rearing frequency, exploratory behavior, and scores in tests having an activity component were depressed for sexually mature offspring who had been exposed to MnO2 both in utero and via suckling. Independent of in utero exposure history, sexually mature offspring reared by mothers exposed to Mn had significantly reduced cerebellum + brain stem mitochondrial Mn levels. Also, sexually mature offspring of mothers exposed to filtered air that were reared by MnO2 -exposed mothers had lower cerebral mitochondrial Mn levels than offspring of control mothers reared by control foster mothers.     

Effects of neonatal capsaicin treatment on nociceptive thresholds in the rat

The responsiveness to noxious thermal, mechanical, and chemical stimuli was examined in adult rats that had been treated neonatally with capsaicin. A range of capsaicin doses was employed to determine whether the neurotoxicity of capsaicin to primary afferent fibers would be manifested behaviorally in a selective effect on nociceptive thresholds to specific stimuli. Animals were given 5 to 100 mg/kg of capsaicin at 2 days of age and were examined 2 to 4 months later using the tail flick and hot plate tests to determine thermal thresholds, the paw pressure test to determine mechanical thresholds, and the formalin test to determine chemical thresholds. Significant impairments of treated animals' responses to all three types of stimuli were found at high doses of capsaicin and at doses which seem to lead to the depletion of only unmyelinated primary afferent fibers. Slightly higher doses of capsaicin were required to increase thermal nociceptive thresholds in the tail flick test as compared with the other tests, and mechanical nociception seemed to be the most sensitive to the effects of capsaicin. At any particular dose of capsaicin, considerable variability was found in the responsiveness of animals to noxious stimuli. This may partly explain the inconsistencies in studies of nociceptive thresholds in capsaicin-treated animals. The results also demonstrate the difficulty of correlating the degree of analgesia exhibited by these animals with the extent of loss of primary afferent fibers or with the depletion of afferent putative peptide transmitters.     

Translocation of phosducin in living neuroblastoma × glioma hybrid cells (NG 108-15) monitored by red-shifted green fluorescent protein

Activation of G protein-coupled receptors triggers translocation of certain proteins from cytoplasm to cell membrane located targets. One of these cytosolic proteins is phosducin (Phd) which has been described to compete with G protein-coupled receptor kinases for Gβγ dimers attached to the cell membrane, thereby attenuating desensitization of activated receptors. These features of protein redistribution prompted us to examine whether stimulation of membrane associated E-prostaglandin receptors coupled to Gs causes Phd to migrate towards the plasma membrane. We made use of enhanced green fluorescence protein (EGFP), a reporter protein, to follow redistribution of Phd both by means of confocal microscopy and biochemical techniques in living neuronal NG 108-15 hybrid cells challenged with prostaglandin E1 (PGE1). The cells were transiently transfected to express Phd fused to the C-terminus of EGFP, or to express EGFP only. Overexpression of the proteins is implied by FACS analysis as well as by western blot technique, and the functional integrity of EGFP-tagged Phd was confirmed by its ability to elevate cAMP accumulation. Time-lapse imaging of single living cells by means of confocal microscopy revealed that exposure to prostaglandin causes EGFP/Phd, which is evenly spread throughout the cell, to relocate towards the membrane within few minutes. Fluorescence associated with the cell nucleus displayed little rearrangement. The principle finding that prostaglandin triggers translocation of Phd from cytosol to the cell periphery was verified with membranes prepared from EGFP/Phd expressing cells. We found maximal concentrations of membrane associated fluorescent material 5 to 7 min upon prostaglandin exposure. The present study reports for living NG 108-15 hybrid cells that PGE1 stimulation causes cytosolic Phd to translocate towards the membrane, where it is believed to bind to G protein subunits such as Gβγ and Gs.