James Meyrick Croker: A Model for Professional Behavior.

The rationale that underpins volunteering has long fascinated behavioral scientists. James Meyrick Croker's personal life, professional career and community engagement conform to the classic twentieth century model for professional behavior. Accordingly, the authors use historical methods of investigation to evaluate the influences on and the legacies from a remarkable contribution to the professions and the community. The narrative demonstrates elements of altruism, collaboration, conviction, compassion, drive, entrepreneurialism, familial and grammar school influence, leadership, pragmatism and vision. Croker's professional and community service was multi-organizational. Concurrent demands on his time warranted discipline, energy and expertise. For the behavioral scientist, achievement, affiliation, nature and nurture appear relevant to the outcome. Available archives provide no evidence of ego-driven motivation. Leadership style was transformational not transactional. Major legacies to the national and state Australian Dental Associations are ADAQ Christensen House (1972-1980), the eventual financial stability for the Australian Dental Association Queensland Branch, formal dental assistant training, policies of the Australian and Queensland Councils of Professions, a notable Goddard Oration and the successful 24th Australian Dental Congress.

Capromorelin increases food consumption, body weight, growth hormone, and sustained insulin-like growth factor 1 concentrations when administered to healthy adult Beagle dogs.

This study's objective was to determine the effects in dogs of oral capromorelin, a ghrelin agonist, at different doses for 7 days on food consumption, body weight and serum concentrations of growth hormone (GH), insulin-like growth factor 1 (IGF-1), and cortisol. Adult Beagles (n = 6) were dosed with placebo BID, capromorelin at 3.0 mg/kg SID, 4.5 mg/kg SID, or 3.0 mg/kg BID. Food consumption, body weight, serum capromorelin, GH, IGF-1, and cortisol were measured at intervals on days 1, 4, 7, and 9. Capromorelin increased food consumption and body weight compared to placebo and caused increased serum GH, which returned to the baseline by 8 h postdose. The magnitude of the GH increase was less on days 4 and 7 compared to Day 1. IGF-1 concentrations increased on Day 1 in capromorelin-treated dogs and this increase was sustained through Day 7. Serum cortisol increased postdosing and returned to the baseline concentrations by 8 h. The magnitude of the increase was less on days 4 and 7 compared to Day 1. A dose of 3 mg/kg was chosen for further study in dogs based on this dose causing increased food consumption and sustained IGF-1 serum concentrations that may increase lean muscle mass when administered over extended periods.

Environmental risk, Oxytocin Receptor Gene (OXTR) methylation and youth callous-unemotional traits: a 13-year longitudinal study.

Youth with high callous-unemotional traits (CU) are at risk for early-onset and persistent conduct problems. Research suggests that there may be different developmental pathways to CU (genetic/constitutional vs environmental), and that the absence or presence of co-occurring internalizing problems is a key marker. However, it is unclear whether such a distinction is valid. Intermediate phenotypes such as DNA methylation, an epigenetic modification regulating gene expression, may help to clarify etiological pathways. This is the first study to examine prospective inter-relationships between environmental risk (prenatal/postnatal) and DNA methylation (birth, age 7 and 9) in the prediction of CU (age 13), for youth low vs high in internalizing problems. We focused on DNA methylation in the vicinity of the oxytocin receptor (OXTR) gene as it has been previously implicated in CU. Participants were 84 youth with early-onset and persistent conduct problems drawn from the Avon Longitudinal Study of Parents and Children. For youth with low internalizing problems (46%), we found that (i) OXTR methylation at birth associated with higher CU (age 13) as well as decreased experience of victimization during childhood (evocative epigenetic-environment correlation; birth-age 7), (ii) higher prenatal parental risks (maternal psychopathology, criminal behaviors, substance use) associated with higher OXTR methylation at birth and (iii) OXTR methylation levels were more stable across time (birth-age 9). In contrast, for youth with high internalizing problems, CU were associated with prenatal risks of an interpersonal nature (that is, intimate partner violence, family conflict) but not OXTR methylation. Findings support the existence of distinct developmental pathways to CU.

Fractional anisotropy distributions in 2- to 6-year-old children with autism.

BACKGROUND: Increasing evidence suggests that autism is a disorder of distributed neural networks that may exhibit abnormal developmental trajectories. Characterisation of white matter early in the developmental course of the disorder is critical to understanding these aberrant trajectories. METHODS: A cross-sectional study of 2- to 6-year-old children with autism was conducted using diffusion tensor imaging combined with a novel statistical approach employing fractional anisotropy distributions. Fifty-eight children aged 18-79 months were imaged: 33 were diagnosed with autism, 8 with general developmental delay, and 17 were typically developing. Fractional anisotropy values within global white matter, cortical lobes and the cerebellum were measured and transformed to random F distributions for each subject. Each distribution of values for a region was summarised by estimating δ, the estimated mean and standard deviation of the approximating F for each distribution. RESULTS: The estimated δ parameter, , was significantly decreased in individuals with autism compared to the combined control group. This was true in all cortical lobes, as well as in the cerebellum, but differences were most robust in the temporal lobe. Predicted developmental trajectories of across the age range in the sample showed patterns that partially distinguished the groups. Exploratory analyses suggested that the variability, rather than the central tendency, component of was the driving force behind these results. CONCLUSIONS: While preliminary, our results suggest white matter in young children with autism may be abnormally homogeneous, which may reflect poorly organised or differentiated pathways, particularly in the temporal lobe, which is important for social and emotional cognition.

A conversation analytic approach to schizophrenic interaction: methodological reflections on disruptions of the common-sense world.

Certain schools of phenomenological psychiatry conceive of schizophrenia as a pathology of common-sense. Ethnomethodological enquiry, with its roots in Schutzian social phenomenology, takes as its domain, topic, and substance of study the ongoing achievement of a common-sense world between social members. Yet, dialogue between psychiatry and ethnomethodological approaches is thin. In this article, we discuss a conversation analytic approach to schizophrenic interaction which has generated and utilized a model of a five-world manifold to frame analyses of talk-in-interaction. 'Worlds' are conceived, after Schutz, as finite domains of meaning, and the model operates as a breach of natural attitude assumptions to examine mechanisms of the constitution of the one-world-in-common of common-sense. It is suggested that certain aspects of schizophrenic talk might receive account in terms of a loss of integration between these five domains of meaning. Conversation Analytic methods were applied to transcripts of audio recordings of psychiatric interviews but encountered hurdles that motivated the broadening of methodological scope. Such hurdles included a weakening of the next turn proof procedure, implicit reification of the schizophrenia construct, and problems of translation presented by the analyst's normative membership encountering non-normative life-worlds of schizophrenic experience. Strategic responses to these hurdles included exploring linkages between phenomenological psychiatry and ethnomethodological approaches, as well as an engagement of ethnomethodological self-reflection and conceptual clarification of the schizophrenia construct in line with Garfinkel's unique adequacy requirement. The manifold model is glossed, and interaction between two of its worlds - a world of concrete, situational immediacies and another of abstract organizations - is explored in more detail via analysis of conversational data. It is suggested that the five-world model, along with further micro-analysis of talk-in-interaction, might have implications in psychiatry for topics such as autism, double bookkeeping, concretism, theories of disturbed indexicality, and insight attribution. We conclude that the consideration of atypical interaction obliges the interaction analyst to take account of their own implicit normative world-frames and that the use of domain-specific top-down models in conjunction with the inductive approach of Conversation Analysis may extend the reach of CA to facilitate productive dialogue with other disciplines.

The role of starburst amacrine cells in visual signal processing.

Starburst amacrine cells (SBACs) within the adult mammalian retina provide the critical inhibition that underlies the receptive field properties of direction-selective ganglion cells (DSGCs). The SBACs generate direction-selective output of GABA that differentially inhibits the DSGCs. We review the biophysical mechanisms that produce directional GABA release from SBACs and test a network model that predicts the effects of reciprocal inhibition between adjacent SBACs. The results of the model simulations suggest that reciprocal inhibitory connections between closely spaced SBACs should be spatially selective, while connections between more widely spaced cells could be indiscriminate. SBACs were initially identified as cholinergic neurons and were subsequently shown to contain release both acetylcholine and GABA. While the role of the GABAergic transmission is well established, the role of the cholinergic transmission remains unclear.

Association with HLA DQ of early onset myasthenia gravis in Southeast Texas region of the United States.

Forty-four Caucasian American myasthenia gravis (MG) patients from Southeast Texas underwent high resolution HLA DQ analysis. For the majority of patients who were late onset or male, no significant associations with DQ were observed. However, associations with DQ increased in female patients and early onset patients. At the allele level, DQB1 *0503, *0604, *0502 and *0402 collectively contributed to a positive association of the DQ locus with early onset MG (EOMG), while individually failing to show significant association. At DQ level, the novel haplotype DQA1*0401:DQB1*0201 was the primary factor in the association of combined DQ loci with early onset. In addition, *0104:*0503, *0102:*0604, *0102:*0502 and *0303:*0402 collectively contributed to the positive association of the haplotype loci. DR3-DQ2.5cis, a well known risk factor for MG in Western Eurasia, was not found associated with disease in any group. For typical EOMG [early onset, no thymoma, anti-acetylcholine receptor (AChR) antibody (Ab) positive] no association with DQA1 locus was found, however DQB1*0604 demonstrated an 'uncorrected' positive association. A few DQ haplotype (DQA1:DQB1) were positively associated with typical EOMG; a positive individual association for *0401:*0201 was complimented by the contributions of *0102:*0604 and *0303:*0402 haplotypes. A small minority of patients that were atypical and EOMG had a strong genetic association with DQA1*0104:DQB1*0503, the group included an anti-MuSK Ab positive and an anti-AChR negative patient. This report finds common ground with European studies regarding MuSK association; however similarities in association for typical early onset disease resembled HLA risk factors in East Asia and Southern Europe.

Trophic effects of skeletal muscle extracts on ventral spinal cord neurons in vitro: separation of a protein with morphologic activity from proteins with cholinergic activity.

Protein factors derived from skeletal muscle separately promote neurite elongation and acetylcholine synthesis in cultured rat ventral spinal neurons. Morphologic factor activity (neurite-inducing activity) is specifically found in rat skeletal muscle and cord neuron extracts, decreases with the postnatal age of the rats from which muscle extract is prepared, and increases in rat hindlimb muscle after 5 d of denervation. Cholinergic factor activity (acetylcholine synthesis-stimulating activity) is found in extracts of rat cerebral cortex and cardiac muscle in addition to spinal cord and skeletal muscle, increases with animal age, and decreases following 5 d of denervation. Biochemically, the factors responsible for these activities differ in their lability to denaturing conditions, apparent molecular weights, isoelectric points, and lectin-binding specificities. Under reducing conditions, morphologic activity is isolated in a single acidic glycoprotein with an Mr of 35,000, while acetylcholine synthesis-stimulating activity is found in multiple species of different molecular weights. Thus, acetylcholine synthesis-promoting activities and neurite growth-promoting activity appear to reside in different molecules. Significant purification of several of these factors has been achieved.

Magnesium pemolone: lack of facilitation in human learning, memory, and performance tests.

Either a placebo or 25 or 37.5 milligrams of magnesium pemoline was administered on a doubleblind basis to three intelligencematched groups of normal, adult males. Learning and 24-hour retention tests included verbal learning, motor learning, and classical conditioning. Short-term memory tests were administered through both the visual and auditory modalities. Arm-hand steadiness and visual reaction time performance tests were included. The only measures revealing significant group differences showed the performance of subjects given pemoline was inferior to that of subjects given a placebo.

Aromatase enzyme activity and sex determination in chickens.

During development, the genotype of the zygote determines the nature of the gonad, which then determines the male or female phenotype. The molecular events underlying this process are just beginning to be defined. A single treatment of chicken embryos with an aromatase inhibitor (which blocks the synthesis of estrogen from testosterone) at a stage when their gonads were bipotential caused genetic females to develop a permanent male phenotype. These sex-reversed females developed bilateral testes that were capable of complete spermatogenesis and had the physical appearance and behavior of normal males. This result identifies aromatase as a key developmental switch in the sex determination of chickens.

Extracts of skeletal muscle increase neurite outgrowth and cholinergic activity of fetal rat spinal motor neurons.

A soluble extract of rat skeletal muscle increased neurite outgrowth and cholinergic activity of dissociated ventral spinal neurons in culture. The effects were concentration-dependent, saturable, and labile in the presence of heat or trypsin. The morphological enhancement was produced only by skeletal muscle extract and decreased with developmental age, whereas the cholinergic enhancement was produced by extracts of cerebral cortex and cardiac and skeletal muscle and did not change with age. These changes were specific for ventral cord neurons, but no species specificity was observed with respect to the muscle source or the neuronal target.

Molecular analysis of the t(2;14) translocation of childhood chronic lymphocytic leukemia.

Two rare cases of chronic lymphocytic leukemia (CLL) in children have been studied; both are associated with a previously undescribed chromosomal translocation [t(2;14) (p13;q32)]. In one patient the translocation was reciprocal and the breakpoint on chromosome 14 occurred just 5' of the C gamma 2 region on the productive immunoglobulin heavy-chain allele. The breakpoint on chromosome 2 does not involve the K locus but lies within an uncharacterized region that coincides with the position of a constitutive fragile site that occurs within normal lymphocytes. Data on the second patient are consistent with these findings and suggest that these cases represent a rare but distinct subgroup of CLL's with a specific cytogenetic change.

Douglas-fir tussock moth: sex pheromone identification and synthesis.

The sex pheromone of the Douglass-fir tussock moth Orgyia pseudotsugata (McDunnough) has been isolated and identified as (Z)-6-heneicosen-11-one. This compound and its E isomer have been synthesized and are highly potent in laboratory bioassays and field trials.

Reverse transcriptase in normal rhesus monkey placenta.

Particles with the morphology of type C virus have been identified from primate placentas by electron microscopy. A reverse transcriptase (RNA-dependent DNA polymerase) was isolated and purified from microsomal pellets of two fresh placentas of rhesus monkeys in the early stages of gestation. This enzyme was biochemically similar yet immunologically distinct from the reverse transcriptases of known tumorigenic type C RNA viruses isolated from primates, but was immunologically related to a reverse transcriptase isolated from a type C virus obtained from normal baboon placenta. These particles may represent endogenous viruses and may function in the transfer of genetic information during embryogenesis.

Inhibition of gonadotropin by delta9-tetrahydrocannabinol:mediation by steroid receptors?

Competition assays for estradiol receptors in cytosol preparations of uteri from rhesus monkeys and humans showed that delta9-tetrahydrocannabinol (THC) does not compete with estradiol for intracellular estrogen recptors. Although isotopically labeled THC bound to macromolecules in uterine cytosol from the rhesus monkey, the binding was not displaced by unlabeled THC, diethylstilbestrol, estradiol, progesterone, cortisol, or 5 alpha-dihydrostestosterone. Scatchard analyses indicated that high-affinity saturable binding of THC to cytosol did not occur. Thus the inhibitory effect of THC on gonadotropin and steroid secretion in primates is not mediated by the interaction of THC with intracellular steroid hormone receptors.

DNA polymerases from RNA tumor viruses and human cells: inhibition by polyuridylic acid.

Polyuridylic acid inhibited DNA polymerases purified from three species of oncornaviruses as well as three out of seven DNA polymerases purified from cells. Viral and cellular DNA polymerases could not be distinguished by polyuridylic acid inhibition, but were easily distinguished by their template preferences in the presence of magnesium.

Human DNA polymerase 3 (R-DNA polymerase): distinction from DNA polymerase I and reverse transcriptase.

DNA polymerase III is an enzyme activity in eukaryotic cells which under certain conditions shows strong preference for polyadenylic acid as template when primed by oligodeoxythymidylate. Its first complete separation from other DNA polymerases in human lymphoblasts is reported. This enzyme is biochemically and immunologically distinct from DNA polymerase I and from viral reverse transcriptase from a primtate type C virus.

Viral and cellular DNA polymerase: comparison of activities with synthetic and natural RNA templates.

Two DNA polymerases purified from normal human lymphocytes are distinguishable from the viral reverse transcriptases of avian myeloblastosis virus and Mason-Pfizer monkey virus by their relative affinity for select templates. In this respect, the activity of the two normal human lymphocyte polymerases closely resembles the activity of Escherichia coli DNA polymerase 1. The viral and cellular DNA polymerases are equally active with the nonspecific template, poly(rA) . poly(dT). Criteria for distinguishing the activity of viral reverse transcriptase are discussed.

A nonpeptidyl growth hormone secretagogue.

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.