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1. The nature, distribution and function of rectifying channels in rat spinal root myelinated axons has been assessed with selective blocking agents and a variety of intracellular and extracellular recording techniques. 2. The electrotonic responses of roots poisoned with tetrodotoxin (TTX) to constant current pulses had fast (rise time much less than 1 ms) and slow components, which were interpreted in terms of Barrett & Barrett's (1982) revised cable model for myelinated nerve. Depolarization evoked a rapid outward rectification (time constant, tau approximately 0.5 ms), selectively blocked by 4-aminopyridine (4AP, 1 mM), and a slow outward rectification (tau approximately 15 ms), selectively blocked by tetraethylammonium (TEA, 1 mM) or Ba2+ (0.5 mM). Hyperpolarization evoked an even slower inward rectification, selectively blocked by Cs+ (3 mM) but not by Ba2+. 3. From the different effects of the blocking agents on the fast and slow components of electrotonus, it was deduced (a) that the inward rectification is a property of the internodal axon, (b) that the slow outward rectifier is present at the nodes, and probably the internodes as well, and (c) that the 4AP-sensitive channels have a minor nodal and a major internodal representation. 4. TEA and Ba2+ reduced the accommodation of roots and fibres not poisoned with TTX to long current pulses, whereas 4AP facilitated short bursts of impulses in response to a single brief stimulus. 5. TEA and Ba2+ also abolished a late hyperpolarizing after-potential (peaking at 20-80 ms), while 4AP enhanced the depolarizing after-potential in normal fibres, and abolished an early hyperpolarizing after-potential (peaking at 1-3 ms) in depolarized fibres. Corresponding to the later after-potentials were post-spike changes in excitability and conduction velocity, which were affected similarly by the blocking agents. Cs+ increased the post-tetanic depression attributable to electrogenic hyperpolarization. 6. The physiological roles of the three different rectifying conductances are discussed. It is also argued that the prominent ohmic 'leak conductance', usually ascribed to the nodal axon, must arise in an extracellular pathway in series with the rectifying internodal axon.
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PMID:Function and distribution of three types of rectifying channel in rat spinal root myelinated axons. 244 52

1. The preceding paper (Van der Kloot, 1988) described a method for estimating the timing of quantal releases during an end-plate current. This period of elevated quantal release is called the early release period or ERP (Barrett & Stevens, 1972b). In the present paper, this deconvolution method is used to study the effects of varying quantal output by extracellular ions, stimulus patterns and drugs. 2. The data were obtained by voltage clamping end-plates in low-Ca2+ high-Mg2+ solutions, or in solutions containing tubocurarine (measuring the decay of the miniature end-plate currents (MEPCs) before curarization and assuming a value for MEPC amplitude after curarization). Data were also obtained by extracellular recording in Ca2+-free solution, using a recording pipette filled with CaCl2 and regulating Ca2+ release with a bias current. The three approaches led to similar conclusions. 3. Quantal release rose during the ERP along a sigmoid curve and reached a maximum after about 1.4 ms at 10 degrees C. This is called the time to peak. Quantal release then fell, following an exponential time course with a time constant of about 1.2 ms (10 degrees C). This is called the time constant for decline. 4. The ERP was followed by further, elevated quantal release, at a much lower rate, which declined over a longer time course. This is called late release. The magnitude of late release appears to be almost independent of the magnitude of release during the ERP, although the deconvolution method is a poor one for determining late release. The remainder of the results therefore focus on the ERP. 5. Increasing [Ca2+]o increased quantal output, and the rate of quantal output. It did not change the time to peak or the time constant of decline. Similarly, replacing Ca2+ with Sr2+ did not alter the time course of the ERP. 6. Two-pulse facilitation increased quantal output without changing the time to peak or the time constant of decline. 7. Quantal output was enhanced still more following a brief series of repetitive nerve stimulations. There was a lengthening of the time to peak; there was no change in the decline. The depression produced by longer series of repetitive stimulations did not change the time course of the ERP. 8. 4-Aminopyridine (4-AP) and dimethylsulphoxide (DMSO) increased quantal output and lengthened the time to peak, without altering the time constant for decline. 9. Adenosine decreased quantal output without altering the time course of the ERP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The kinetics of quantal releases during end-plate currents at the frog neuromuscular junction. 285 24

The use of end-plate current (e.p.c.) latency measurements to estimate the time course of the stochastic probabilistic process governing evoked release was investigated in the sciatic nerve-sartorius muscle preparation of the frog, Rana pipiens. We also examined the possibility that the release of a quantum depresses or enhances the subsequent release of additional quanta. Muscle end-plates were voltage clamped at 3-4 degrees C. Quantal release was restricted to a short, or localized, region of the nerve terminal using Ca2+-free, EGTA Ringer solution and a Ca2+-filled micropipette. The number of e.p.c.s containing 0, 1, 2, etc. quanta were totalled and compared to numbers predicted using Poisson's theorem. The differences between the actual and predicted numbers of events were not significant at the nineteen junctions studied (P less than 0.05). The latency of the first quantum observed in several hundred e.p.c.s was measured and used to calculate an estimate, alpha 1(t), of the time-dependent, probabilistic process, alpha (t), governing all evoked quantal release (Barrett & Stevens, 1972b). In three experiments, all quantal latencies were measured to obtain the actual alpha (t). The alpha 1(t) function gave an excellent approximation of alpha (t) (P greater than 0.2), in real and simulated latency data. The latency of the second quantum in the e.p.c.s was measured and used to provide another estimate, alpha 2(t), of alpha (t). The alpha 2(t) function was lower (depressed) during the first few milliseconds of the evoked release period, relative to alpha 1(t). The difference was significant (P greater than 0.01) in all experiments. Our measurement procedures were tested using computer-generated 'e.p.c.s' containing randomly occurring 'quanta'. These tests showed that the early depression was due to inadequate detection of the second quantum in the e.p.c.s. The effect of Sr2+ on evoked release was examined using double-barrelled pipettes containing 1 M-SrCl2 and CaCl2 solutions. The major result was that the durations of alpha 1(t) and alpha 2(t) were equally lengthened in Sr2+, relative to Ca2+.
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PMID:Estimating the time course of evoked quantal release at the frog neuromuscular junction using end-plate current latencies. 348 94

Although many types of behavioral and emotional disorders are prevalent in children with developmental delays, the phenomenology of childhood depression in this population remains poorly understood. This study examined the relationships among symptoms of depression, child problem behaviors, and parenting stress in a sample of 29 children with developmental delays. Results supported the usefulness of the Children's Depression Inventory (CDI) in assessing depression in these children initially reported by Matson, Barrett, and Helsel (1988). Parent ratings from the CDI were significantly associated with maternal depression, an index of DSM-III-R depression criteria, and negative self-image, anxiety, and conduct problems in children. A matched subsample of children (n = 12) with high versus low depression ratings revealed significant differences in total scores from the Parenting Stress Index (Abidin, 1986) and the index of DSM-III-R depression criteria. Together, these data suggest that children with developmental delays exhibit a similar pattern of symptoms and associated characteristics to those found in normal children with diagnoses of depression.
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PMID:Parenting stress and depression in children with mental retardation and developmental disabilities. 752 19

Looking at the field as a whole through metaanalysis, Shadish et al concluded (based on 162 studies) that marital and family therapies were significantly more effective than no treatment and at least as effective as other forms of psychotherapy. Although these reviews and others are positive, individual studies raise many questions. For instance, based on research findings, family treatments increasingly have become standard care for patients with schizophrenia. It remains unclear what degree and type of family involvement is needed for which patients at which stage of their disorder. In the area of anxiety and depression, there are too few studies to make any strong conclusion. Although investigators such as Barrett, Cobham, and Diamond have produced some positive results, the Lewinsohn and Clark studies fail to demonstrate the added benefit of family involvement. Although Brent's study showed CBT to reduce depression faster, family therapy and supportive therapy did just as well in the long run, and family conflict was a strong risk factor for relapse. In the area of anorexia, Russell and Robins produced strong results from family interventions, whereas Geist found no difference between different types of family interventions. Family treatments for obesity have been inconsistent. In a metaanalysis of 41 studies, parental involvement did not contribute significantly to outcomes. In the Epstein study, however, which included 5- and 10-year follow-up, the results of family intervention were impressive. Although many of these studies can be cited for various methodologic flaws, the most consistent problem is that sample sizes are too small to detect difference between two or more active treatments. The most consistent findings (and most well-done, large studies) that support the efficacy of family-based interventions are done with externalizing problems. Work groups led by Patterson, Eisenstadt, Webster-Stratton, Alexander, and Henggeler all have produced impressive reductions of oppositional and antisocial behavior. Clinical programs that treat these populations without using a family-based intervention as at least a component of a treatment package are seriously ignoring the findings of contemporary intervention science. Programs of research by Henggeler, Szapocznik, and Liddle demonstrate similarly impressive results for substance abusing adolescents. Although preliminary results from the Dennis et al study suggest that various treatment approaches may benefit this population. Family interventions have had less success in reducing ADHD symptoms, yet these psychosocial treatments have been essential in reducing much of the family and school behavior problems associated with this disorder. Many investigators would agree that a combined medication and family treatment approach may be the treatment of choice for children with ADHD. In fact, many studies across various disorders suggest that patients respond best to comprehensive treatment packages, of which a family treatment is at least one component. Although the data are promising, many challenges lie ahead. Although collectively many family intervention studies exist, many disorders lack enough rigorous and large-scale investigations to make any strong conclusions. Kazdin argues that sample sizes of 150 are essential to detect significant differences between active treatments, and few of the reviewed studies include these kinds of patient numbers. Furthermore, not enough committed and sophisticated family treatment researchers have carried out some of the major studies. For example, the Brent study on depression and the Barkley study of ADHD, although testing family approaches, lacked well-developed and published treatment manuals, a demonstration of the necessary expertise to supervise these treatments, and data about training and adherence to these models. Although the absence of expertise limits investigator allegiance biases, treatment development and modification are essential for tailoring family treatments to target family processes specific to each disorder. Investigators such as Patterson and Liddle have invested great effort in rigorously dismantling the treatment process, identifying and refining essential ingredients, and repackaging more potent treatment protocols. This process has paid off well. Programmatic treatment development is needed for many disorders to address myriad questions. What are the essential disorder-specific family processes that should be targeted by interventions? Hostility, criticism, communication, attachment and autonomy, attributional sets, and behavior management are important processes of family life, but each may have more relative importance for specific disorders. With a greater understanding of these processes, treatments could be tailored to target these mechanisms more efficiently and effectively. (ABSTRACT TRUNCATED)
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PMID:Current status of family intervention science. 1144 17

The aqueous extract of Centranthus longiflorus ssp. longiflorus (CLE) was investigated for sedative, anticonvulsant and behaviour modifying activity using thiopental sleeping, caffeine induced convulsion and forced swimming depression tests. When the effects of the aqueous extract of CLE (100 mg/kg) was compared to diazepam, it showed similar sedative and anticonvulsant effects to those produced by diazepam (5 mg/kg).
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PMID:Sedative, anticonvulsant and behaviour modifying effects of Centranthus longiflorus ssp. longiflorus: a study of comparison to diazepam. 1222 98

Gene expression profiles in the cortex of adult Long-Evans rats as a function of a stressful social loss and victory in inter-male fighting encounters were examined. This social dominance and subordination model has been postulated to simulate early changes in the onset of depression in the losers. Microarrays were fabricated containing 45mer oligonucleotides spotted in quadruplicate and representing 1178 brain-associated genes. Dynamic range, discrimination power, accuracy and reproducibility were determined with standard mRNA "spiking" studies. Gene expression profiles in dominant and subordinate animals were compared using a "universal" reference design [Churchill GA (2002) Fundamentals of experimental design for cDNA microarrays. Nat Genet 32 (Suppl):490-495]. Data were analyzed by significance analysis of microarrays using rank scores [Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98:5116-5121; van de Wiel MA (2004) Significance analysis of microarrays using rank scores. Kwantitatieve Methoden 71:25-37]. Ontological analyses were then performed using the GOMiner algorithm [Zeeberg BR, Feng W, Wang G, Wang MD, Fojo AT, Sunshine M, Narasimhan S, Kane DW, Reinhold WC, Lababidi S, Bussey KJ, Riss J, Barrett JC, Weinstein JN (2003) GoMiner: a resource for biological interpretation of genomic and proteomic data. Genome Biol 4(4):R28]. And finally, genes of special interest were further studied using quantitative reverse transcriptase polymerase chain reaction. Twenty-two transcripts were statistically significantly differentially expressed in the neocortex between dominant and subordinate animals. Ontological analyses revealed that significant gene changes were clustered primarily into functional neurochemical pathways associated with protein biosynthesis and cytoskeletal dynamics. The most robust of these were the increased expression of interleukin-18, heat shock protein 27, beta3-tubulin, ribosome-associated membrane protein 4 in subordinate animals. Interleukin-18 has been found to be over-expressed in human depression and panic disorder as well as other physiological stress paradigms [Takeuchi M, Okura T, Mori T, Akita K, Ohta T, Ikeda M, Ikegami H, Kurimoto M (1999) Intracellular production of interleukin-18 in human epithelial-like cell lines is enhanced by hyperosmotic stress in vitro. Cell Tissue Res 297(3):467-473] and heat shock proteins have been shown to be involved in the pathogenesis of many neurodegenerative and psychiatric disorders [Iwamoto K, Kakiuchi C, Bundo M, Ikeda K, Kato T (2004) Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders. Mol Psychiatry 9(4):406-416; Pongrac JL, Middleton FA, Peng L, Lewis DA, Levitt P, Mirnics K (2004) Heat shock protein 12A shows reduced expression in the prefrontal cortex of subjects with schizophrenia. Biol Psychiatry 56(12):943-950]. Thus, the gene expression changes that we have observed here are consistent with and extend the observations found in the clinical literature and link them to the animal model used here thereby reinforcing its use to better understand the genesis of depression and identify novel therapeutic targets for its treatment.
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PMID:Modeling depression: social dominance-submission gene expression patterns in rat neocortex. 1628 86

This study evaluated the long-term effectiveness of the FRIENDS Program in reducing anxiety and depression in a sample of children from Grade 6 and Grade 9 in comparison to a control condition. Longitudinal data for Lock and Barrett's (2003) universal prevention trial is presented, along with data from 12-month follow-up to 24- and 36-month follow-up. Results of this study indicate that intervention reductions in anxiety reported in Lock and Barrett were maintained for students in Grade 6, with the intervention group reporting significantly lower ratings of anxiety at long-term follow-up. A significant Time x Intervention Group x Gender Effect on Anxiety was found, with girls in the intervention group reporting significantly lower anxiety at 12-month and 24-month follow-up but not at 36-month follow-up in comparison to the control condition. Results demonstrated a prevention effect with significantly fewer high-risk students at 36-month follow-up in the intervention condition than in the control condition. Results are discussed within the context of prevention research.
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PMID:Long-term outcomes of an Australian universal prevention trial of anxiety and depression symptoms in children and youth: an evaluation of the friends program. 1683 77

Observations about the natural history of aging in Cornelia de Lange syndrome (CdLS) are made, based on 49 patients from a multidisciplinary clinic for adolescents and adults. The mean age was 17 years. Although most patients remain small, obesity may develop. Gastroesophageal reflux persists or worsens, and there are early long-term sequelae, including Barrett esophagus in 10%; other gastrointestinal findings include risk for volvulus, rumination, and chronic constipation. Submucous cleft palate was found in 14%, most undetected before our evaluation. Chronic sinusitis was noted in 39%, often with nasal polyps. Blepharitis improves with age; cataracts and detached retina may occur. Decreased bone density is observed, with occasional fractures. One quarter have leg length discrepancy and 39% scoliosis. Most females have delayed or irregular menses but normal gynecologic exams and pap smears. Benign prostatic hypertrophy occurred in one male prior to 40 years. The phenotype is variable, but there is a distinct pattern of facial changes with aging. Premature gray hair is frequent; two patients had cutis verticis gyrata. Behavioral issues and specific psychiatric diagnoses, including self-injury, anxiety, attention-deficit disorder, autistic features, depression, and obsessive-compulsive behavior, often worsen with age. This work presents some evidence for accelerated aging in CdLS. Of 53% with mutation analysis, 55% demonstrate a detectable mutation in NIPBL or SMC1A. Although no specific genotype-phenotype correlations have been firmly established, individuals with missense mutations in NIPBL and SMC1A appear milder than those with other mutations. Based on these observations, recommendations for clinical management of adults with CdLS are made.
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PMID:Natural history of aging in Cornelia de Lange syndrome. 1764 42

We examined the factor structure of the Neuroticism scale of the Eysenck Personality Questionnaire (EPQ-R-N; S. B. G. Eysenck, Eysenck & Barrett, 1985) and its factor invariance across sex and racial/ethnic groups in a sample of 1,979 adolescents. Using confirmatory factor analyses, we compared a hierarchical model to previous models of the EPQ-R-N and to single-factor and 3-factor structures. The hierarchical factor structure in which a general factor coexists with 3 group factors (depression, social concerns, and worry) was superior to alternative models. The general factor accounted for more than 60% of the variance in EPQ-R-N total scores and was invariant across sex and ethnicity. The 3 group factors varied across ethnicity and sex. We discuss the implications of these findings for conceptualization and assessment of neuroticism using the EPQ-R-N.
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PMID:Evaluating the invariance of the factor structure of the EPQ-R-N among adolescents. 1844 97


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