Calcium in development: from ion transients to gene expression.
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14-3-3 Proteins↗
Biomedical subjects
A L Miller
Publications and source records attributed to A L Miller.
Effects of chronic stimulation on auditory nerve survival in ototoxically deafened animals.
For almost 10 years, chronic stimulation has been known to affect spiral ganglion cell (SGC) survival in the deaf ear. However, the reported effects of chronic stimulation vary across preparations and studies. In this review, the effects of chronic stimulation on the deafened auditory periphery are examined, and variables that may impact on the efficacy of chronic stimulation are identified. The effects of deafening on the unstimulated peripheral and central auditory system are also described, as the deafened, unstimulated system is the canvas upon which stimulation-mediated effects are imposed. Discrepancies in the effects of chronic stimulation across studies may be attributable in large part to the combined effects of the deafening method and the post-deafening delay prior to chronic stimulation, which vary across studies. Emphasis is placed on the need to consider the natural progression of SGC loss following deafening in the absence of chronic stimulation, as the rate of SGC loss almost certainly affects both the efficacy of stimulation, and the impact of any delay between deafening and initiation of stimulation. The differences across preparations complicate direct comparison of protective efficacy of stimulation. At the same time, these differences can be used to our advantage, aiding characterization of the effects of different factors on the efficacy of chronic stimulation as a neuroprotective intervention.
Animals↗
Cochlear implant thresholds: comparison of middle latency responses with psychophysical and cortical-spike-activity thresholds.
The electrically evoked middle latency response (EMLR) is a potentially useful measure of activation of the auditory system by a cochlear prosthesis. The present study compared cochlear prosthesis thresholds determined using EMLR with thresholds determined for psychophysical detection and for spike activity in cortical neurons. In systemically deafened guinea pigs, the difference between EMLR and psychophysical threshold level varied, with differences ranging from -4.6 dB (EMLR threshold more sensitive) to +10.7 dB (psychophysical threshold more sensitive) across animals and phase durations. Threshold differences between EMLR and auditory cortex neural spike responses were similar in magnitude and range (-6 to +15 dB) to those seen for EMLR vs. psychophysical thresholds. These ranges are comparable to the behavioral operating range for a given condition. In 3 of 12 subjects, the EMLR was absent for some or all electrode configurations tested, even at levels well above the threshold for psychophysical detection or cortical neuronal response. These results suggest that neither the EMLR thresholds nor cortical neuronal spike thresholds are an adequate substitute for psychophysical measures of threshold. While not sufficient for use in place of psychophysical measures, EMLR threshold level is strongly correlated with psychophysical threshold level across subjects (R(2)=0.82). Interestingly, plots of thresholds vs. phase duration were roughly parallel for psychophysical and EMLR thresholds, in contrast to the divergence of psychophysical and more peripheral (e.g., electrically evoked auditory brainstem response) evoked neural threshold vs. phase duration functions.
Action Potentials↗
Evidence-based pharmacologic treatment for people with severe mental illness: a focus on guidelines and algorithms.
Medication treatment of severe mental illness has been advanced and complicated by the introduction of numerous therapeutic agents. Practice guidelines based on research evidence have been developed to help clinicians make complex decisions. Studies of usual care suggest an important potential role for guidelines in improving the quality of medication treatment for people with severe mental illness. The authors review current evidence-based guidelines for medication treatment of persons with severe mental illness. Four categories of guidelines are described: recommendations, comprehensive treatment options, medication algorithms, and expert consensus. The authors note that more research is needed on optimal next-step strategies and the treatment of patients with comorbidity and other complicating problems. They discuss barriers to the implementation of guidelines, and they observe that the potential of guidelines and algorithms to promote evidence-based medication treatment for persons with severe mental illness depends on refinement of tools, progress in research, and cooperation of physicians, nonphysician clinicians, administrators, and consumers and family members.
Depressive Disorder↗
The etiologies, pathophysiology, and alternative/complementary treatment of asthma.
A chronic inflammatory disorder of the respiratory airways, asthma is characterized by bronchial airway inflammation resulting in increased mucus production and airway hyper-responsiveness. The resultant symptomatology includes episodes of wheezing, coughing, and shortness of breath. Asthma is a multifactorial disease process with genetic, allergic, environmental, infectious, emotional, and nutritional components. The underlying pathophysiology of asthma is airway inflammation. The underlying process driving and maintaining the asthmatic inflammatory process appears to be an abnormal or inadequately regulated CD4+ T-cell immune response. The T-helper 2 (Th2) subset produces cytokines including interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, and IL-13, which stimulate the growth, differentiation, and recruitment of mast cells, basophils, eosinophils, and B-cells, all of which are involved in humoral immunity, inflammation, and the allergic response. In asthma, this arm of the immune response is overactive, while Th1 activity, generally corresponding more to cell-mediated immunity, is dampened. It is not yet known why asthmatics have this out-of-balance immune activity, but genetics, viruses, fungi, heavy metals, nutrition, and pollution all can be contributors. A plant lipid preparation containing sterols and sterolins has been shown to dampen Th2 activity. Antioxidant nutrients, especially vitamins C and E, selenium, and zinc appear to be necessary in asthma treatment. Vitamins B6 and B12 also may be helpful. Omega-3 fatty acids from fish, the flavonoid quercetin, and botanicals Tylophora asthmatica, Boswellia serrata and Petasites hybridus address the inflammatory component. Physical modalities, including yoga, massage, biofeedback, acupuncture, and chiropractic can also be of help.
Air Pollution↗
Calcium signalling during zebrafish embryonic development.
Calcium signals appear throughout the first 24 hours of zebrafish development. These begin at egg activation, then continue to be generated throughout the subsequent zygote, cleavage, blastula, gastrula, and segmentation periods. They are thus associated with the major phases of pattern formation: cell proliferation, cell differentiation, axis determination, the generation of primary germ layers, the emergence of rudimentary organ systems, and therefore the establishment of the basic vertebrate body plan. When signals need to be transmitted across significant distances they take the form of waves, either intracellular waves when the cell size is large, or later in development when the cell size is reduced, intercellular waves. We will consider both types of calcium signals and their integration into signalling networks, and discuss their possible functions and developmental significance with regard to pattern formation. BioEssays 22:113-123, 2000.
Animals↗
Youth suicidal behavior: assessment and intervention.
In this article, the authors review the research on risk assessment of suicidal adolescents and describe the small body of randomized-clinical-treatment trials for this population. Research has yielded a fairly consistent set of direct and indirect risk factors for suicidal behavior in adolescents. The authors describe a variety of measures commonly used to assess these risk factors. Treatment studies targeting suicide are sparse for all ages. In the adult literature, evidence suggests clozapine, depot flupenthixol, lithium, and dialectical behavior therapy (DBT) are significantly more effective in decreasing suicidal behavior than placebo or Treatment as Usual. For adolescents, it is difficult to draw conclusions about treatment efficacy. In general, control conditions are just as effective at reducing suicidal behavior as experimental conditions. While some novel interventions for suicidal adolescents are described, there is a desperate need for more research to be conducted in order to advance this burgeoning field.
Adolescent↗
MACI personality scale profiles of depressed adolescent suicide attempters: a pilot study. Million Adolescent Clinical Inventory.
Employing the Millon Adolescent Clinical Inventory (MACI), we examined differences in the maladaptive personality style profiles of clinically referred, depressed adolescents presenting with (n = 26) and without (n = 23) a history of previous suicide attempts. Relative to the comparison group, adolescent attempters experienced more severe overall levels of personality dysfunction. At the trait level, attempters obtained higher scores on the forceful and borderline tendency scales and lower scores on the submissive and conforming scales of the MACI, reflecting negative mood regulation deficits (e.g., anger control problems) and persistently high levels of aggressive impulsivity. These preliminary findings suggest that MACI personality scales may be useful in discriminating adolescents with and without previous suicidal behavior, especially among depressed outpatient samples.
Adolescent↗
Evidence-based treatment of schizophrenia.
People with schizophrenia can be helped greatly with pharmacologic and psychosocial interventions that are known to be effective. Several interventions are now supported by research: use of medications following specific guidelines, training in illness self-management, case management based on principles of assertive community treatment, family psychoeducation, supported employment, and integrated substance abuse treatment. However, few patients actually receive these evidence-based interventions because they are not provided in routine mental health settings. Therefore, implementing effective treatments in mental health treatment programs is a critical challenge for the field. We review the six areas of evidence-based treatment of schizophrenia, as well as knowledge regarding implementation of mental health programs in routine practice settings.
Antipsychotic Agents↗
Effects of time after deafening and implantation on guinea pig electrical detection thresholds.
Changes in detection threshold level as a function of time after deafening and implantation have been described previously in macaque [Pfingst, 1990] and human [Skinner et al., 1995] cochlear implant subjects. Characterization of the mechanisms underlying these changes will contribute to our understanding of the anatomical and physiological factors affecting electrical stimulus detection. In addition, understanding the time course of early threshold changes is essential to the interpretation of acute physiological studies of cochlear implants. To better characterize time-dependent threshold changes, we monitored changes in guinea pig psychophysical electrical detection thresholds with time after deafening and cochlear implantation. Threshold levels for 100 Hz sinusoidal bursts were initially unstable over the first 30 days post-surgery (DPS), after which thresholds stabilized. At longer intervals (>100 DPS), increases (>10 dB) in threshold level were observed for 100 Hz sinusoids in three of 11 cases. These changes were transient in one case and long-term in two cases. The time course of threshold change, both early and late, could not be explained on the basis of changes in spiral ganglion cell survival. The guinea pig seems to be an ideal preparation for studies of this nature, because threshold changes are similar in type, but accelerated in time course, relative to those observed in primates.
Animals↗
Differential protective effects of neurotrophins in the attenuation of noise-induced hair cell loss.
The protective efficacy of neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) at 1 or 10 microg/ml was assessed in guinea pigs exposed to 4 kHz octave band noise at 115 dB SPL for 5 h. BDNF, NT-3 or artificial perilymph was delivered to the scala tympani via a mini-osmotic pump, beginning 4 days prior to noise exposure and continuing for 1 week post-exposure. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold, and histologically by outer hair cell (OHC) survival. There was a statistically significant increase in OHC survival and a decrease in ABR threshold shift in animals receiving NT-3 at a concentration of 10 microg/ml. In animals receiving 1 microg/ml NT-3, there was a significant increase in OHC survival in the first row of OHC, but no significant change in ABR threshold, relative to control animals. In animals treated with BDNF, no significant functional or histological protection was observed. The protection afforded by NT-3 (10 microg/ml) treatment was similar in magnitude to that reported previously with glial cell line-derived neurotrophic factor and suggests that several factors may be involved in the protective response.
Animals↗
Emotional expressiveness during peer conflicts: a predictor of social maladjustment among high-risk preschoolers.
Preschool boys' emotional displays during conflicts with mixed-sex peers were related to individual differences in peer sociometric status and teacher ratings of disruptive behavior. Participants were 60 4- to 5-year old boys from low-income families who were videotaped with a small group of classmates in a Head Start preschool classroom. Conflicts were identified and emotional displays were coded from videotape. Results indicated that conflicts were more negative in emotional tone at the end than at the beginning of the year. Furthermore, children tended to mirror each others' emotional displays at the end but not the beginning of the preschool year. In addition, gleeful taunting, a form of emotional aggression, more strongly predicted negative peer nominations and teacher ratings than anger, suggesting that anger may be a more socially accepted form of emotional expression during conflicts among preschool-age children. Implications and directions for future research and interventions are discussed.
Aggression↗
Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity.
Gentamicin administration often results in cochlear and/or vestibular hair cell loss and hearing and balance impairment. It has been demonstrated that adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) can protect cochlear hair cells against ototoxic injury. In this study, we evaluated the protective effects of adenovirus-mediated overexpression of GDNF against gentamicin ototoxicity. An adenovirus vector expressing the human GDNF gene (Ad.GDNF) was administered into the scala vestibuli as a rescue agent at the same time as gentamicin, or as a protective agent, 7 days before gentamicin administration. Animals in the Rescue group displayed hearing thresholds that were significantly better than those measured in the Gentamicin or Ad.LacZ/Gentamicin groups. In the Protection group, Ad.GDNF afforded significant preservation of utricular hair cells. The data demonstrated protection of the inner ear structure, and rescue of the inner ear structure and function against ototoxic insults. These experiments suggest that inner ear gene therapy may be developed as a clinical tool for protecting the ear against environmentally induced insults.
Adenoviridae↗
On the mechanism of ooplasmic segregation in single-cell zebrafish embryos.
It has been previously shown that localized elevations of free cytosolic calcium are associated with a morphological contraction in the forming blastodisc and animal hemisphere cortex during ooplasmic segregation in zebrafish zygotes. It was subsequently proposed, in a hypothetical model, that these calcium transients might be linked to the contraction of a cortically located actin microfilament network as a potential driving force for segregation. Here, by labeling single-cell embryos during the major phase of segregation with rhodamine-phalloidin, direct evidence is presented to indicate that the surface contraction was generated by an actin-based cortical network. Furthermore, while zygotes incubated with colchicine underwent normal ooplasmic segregation, those incubated with cytochalasin B did not generate a constriction band or segregate to form a blastodisc. During segregation at the single-cell stage, ooplasm simultaneously moved in two directions: toward the blastodisc within the so-called axial streamers, and toward the vegetal pole in the peripheral ooplasm. The velocities of both axial and peripheral streaming movements are reported. By injection of a fluorescein isothiocyanate (FITC)-labeled 2000 kDa dextran into the peripheral ooplasm it was demonstrated that a portion of it feeds into the bases of the extending streamers, which helps to explain the lack of accumulation of ooplasm at the vegetal pole. These new data were incorporated into the original model to link the bipolar ooplasmic movements with the calcium-modulated, actin-mediated contraction of the animal hemisphere cortex as a means of establishing and driving ooplasmic segregation in zebrafish.
Actins↗
Do specific neurocognitive deficits predict specific domains of community function in schizophrenia?
We examined whether specific neurocognitive deficits predicted specific domains of community outcome in 40 schizophrenic patients. Neuropsychological assessments were conducted before hospital discharge, and measures of functional outcome were obtained 1 to 3.5 years later. A priori hypotheses were generated based upon a recent review by Green (Green MF [1996] What are the functional consequences of neurocognitive deficits in schizophrenia? American Journal of Psychiatry, 153(3):321-330). As hypothesized, verbal memory predicted all measures of community outcome, vigilance predicted social outcomes, and executive functioning predicted work and activities of daily living (ADLs). However, in addition to the predicted relationships, many other associations were found between neuropsychological test scores and adaptive function. Furthermore, both cognitive and functional measures were intercorrelated. If deficits in adaptive functioning are neurocognitively multi-determined, utilizing compensatory strategies to bypass multiple areas of cognitive impairment may be more efficient than cognitive remediation in improving community outcomes.
Activities of Daily Living↗
Randomized controlled trial of the use of compensatory strategies to enhance adaptive functioning in outpatients with schizophrenia.
OBJECTIVE: Cognitive adaptation training is a novel psychosocial treatment approach designed to improve adaptive functioning by using compensatory strategies in the home or work environment to bypass the cognitive deficits associated with schizophrenia. The authors tested the effect of cognitive adaptation training on level of adaptive functioning in outpatients with schizophrenia. METHOD: Forty-five patients with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned for 9 months to one of three treatment conditions: 1) standard medication follow-up, 2) standard medication follow-up plus cognitive adaptation training, and 3) standard medication follow-up plus a condition designed to control for therapist time and provide environmental changes unrelated to cognitive deficits. Comprehensive assessments were conducted every 3 months by raters who were blind to treatment condition. RESULTS: Significant differences were found between the three treatment groups in levels of psychotic symptoms, motivation, and global functioning at the end of the 9-month study period. Patients in the cognitive adaptation training group overall had higher levels of improvement, compared with those in the remaining treatment conditions. In addition, the three groups had significantly different relapse rates over the 9-month study: 13% for the cognitive adaptation training group, 69% for the group in which therapist time and environmental changes were controlled, and 33% for the group who received standard follow-up only. CONCLUSIONS: Compensatory strategies may improve outcomes for patients with schizophrenia.
Adult↗
Imaging patterns of calcium transients during neural induction in Xenopus laevis embryos.
Through the injection of f-aequorin (a calcium-sensitive bioluminescent reporter) into the dorsal micromeres of 8-cell stage Xenopus laevis embryos, and the use of a Photon Imaging Microscope, distinct patterns of calcium signalling were visualised during the gastrulation period. We present results to show that localised domains of elevated calcium were observed exclusively in the anterior dorsal part of the ectoderm, and that these transients increased in number and amplitude between stages 9 to 11, just prior to the onset of neural induction. During this time, however, no increase in cytosolic free calcium was observed in the ventral ectoderm, mesoderm or endoderm. The origin and role of these dorsal calcium-signalling patterns were also investigated. Calcium transients require the presence of functional L-type voltage-sensitive calcium channels. Inhibition of channel activation from stages 8 to 14 with the specific antagonist R(+)BayK 8644 led to a complete inhibition of the calcium transients during gastrulation and resulted in severe defects in the subsequent formation of the anterior nervous system. BayK treatment also led to a reduction in the expression of Zic3 and geminin in whole embryos, and of NCAM in noggin-treated animal caps. The possible role of calcium transients in regulating developmental gene expression is discussed.
Aequorin↗
ADHD, Ritalin, and big brother.
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Attention Deficit Disorder with Hyperactivity↗