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PubMed1999

Development of catecholaminergic neurons in the pond snail, Lymnaea stagnalis: II. Postembryonic development of central and peripheral cells.

Catecholamines have long been thought to play important roles in different mollusc neural functions. The present study used glyoxylate- and aldehyde-induced histofluorescence to identify central and peripheral catecholaminergic neurons in the snail Lymnaea stagnalis. The majority of these cells were also found to react to antibodies raised against tyrosine hydroxylase. A minority of the catecholaminergic neurons, however, exhibited no such immunoreactivity. The number of central catecholaminergic neurons nearly doubled (from about 45 to about 80 cells) during the first 2-3 days of postembryonic development. Thereafter, catecholaminergic neurons again doubled in number and generally grew by about 100-200% in soma diameter as the snails grew by 1,000% in overall linear measurements. In contrast to the relatively meager addition of central catecholaminergic neurons, several thousand catecholaminergic somata were added to different peripheral tissues during postembryonic development. These small, centrally projecting neurons were particularly concentrated in the lips, esophagus, anterior margin of the foot, and different regions of the male and female reproductive tracts. Chromatographic analyses indicated that dopamine was the major catecholamine present in the central ganglia, foot, and esophagus, although detectable levels of norepinephrine (approximately 20% of dopamine levels) were also found in the ganglia. The total content but not the concentration of dopamine increased within the tissue samples during postembryonic development. The companion study (Voronezhskaya et al. [1999] J. Comp. Neurol. 404:285-296) and the present study furnish a complete description of central and peripheral catecholaminergic neurons from their first appearance in early embryonic development to adulthood.

Animals↗

PubMed1993

Gene expression of CD24 core peptide molecule in developing brain and developing non-neural tissues.

CD24 is a signal transducing molecule on the surface of most human B cells, murine immature T cells, myeloid and erythroid lineage cells. We isolated rat CD24 gene from embryonic brain cDNA library and characterized the gene expression during rat embryogenesis. Rat CD24 cDNA is homologous to murine and human CD24 gene with respect to the structure of signal peptide, N-glycosylation sites, and possible glycosyl phosphatidylinositol (GPI) linker attaching site, suggesting that rat CD24 is a transducing glycoprotein anchoring membrane via GPI linker. In the developing embryo, in situ hybridization analyses revealed that CD24 transcript was detected in primitive ectoderm, mesoderm, and ventral endoderm of day 9 postcoitum (p.c.) embryo. In central nervous systems CD24 transcript was strongly expressed in postmitotic cells of spinal cord, hindbrain, midbrain, and forebrain from day 11 p.c. embryo to day 21 p.c. embryo but was dramatically down regulated in adult brain. Furthermore, expression was also detected in epithelium during development of non-neural tissues, such as intestinal mucosal epithelium, nasal epithelium, ductal epithelium of salivary gland, bronchial epithelium, renal tubular epithelium, and hair follicles. In tooth development, where correct epithelium requires epithelial-mesenchymal interactions, CD24 mRNA was specifically induced in mesenchymal cells differentiating into odontoblast in dental papilla, suggesting the pivotal role of CD24 molecule in cell differentiations in vivo. We suggest that CD24 gene may encode the core peptide molecule of 31 kDa GPI linked molecule which has been known to be important in the migration of neurons on astroglial processes during development.

Amino Acid Sequence↗

PubMed1985

A comparative analysis of the development of the primary somatosensory cortex: interspecies similarities during barrel and laminar development.

The development of the barrels and layers II-V was examined in Nissl-stained preparations of the primary somatosensory cortex in six species--hamster, mouse, rat, gerbil, rabbit, and guinea pig--that have increasingly longer gestation periods. The barrels and layers II-V begin to differentiate postnatally during the first week postpartum in the hamster, mouse, rat and gerbil; perinatally in the rabbit; and approximately 4 weeks prenatally in the guinea pig. The structure of the barrels and layers II-V is similar at the onset of their differentiation in each species, even though there are interspecies differences in the mature structure of the barrels and layer V. The rate of the initial differentiation of the barrels and layers II-V is also similar in each species, even though there are considerable interspecies differences in the duration of the preceding period of development. In each species, layer V begins to differentiate first from the cortical plate and, within 1 or 2 days, contains sublayers that eventually disappear in the rabbit and guinea pig. About 3 days after the initial differentiation of layer V, layers II-IV begin to differentiate, seemingly simultaneously, causing the cortical plate to have a trilaminar appearance. Barrels are first evident just before the appearance of the trilaminar plate in hamsters; concomitant with the trilaminar plate in mice, rats, and guinea pigs; and just after the trilaminar plate in gerbils and rabbits. Septa appear 1 or 2 days after the barrels except in rabbits, which never have septa. Barrel maturation proceeds rapidly after the initial appearance in all species except the hamster, in which continued maturation seems to be delayed until the appearance of the trilaminar plate. The barrels in immature rats and rabbits become more prominent than they will eventually be in the adults. Our results indicate a close and rapid developmental affiliation between layers II-V, especially layers II-IV, that seems quite separate from the development of layers I and VI. However, barrel development and differentiation of layers II-IV seem to be closely, but independently initiated. Secondary remodeling occurs in layer V and the barrels of some species.

Animals↗

PubMed2001

Developing decision support systems for integrated coastal management in the tropics: is the ICM decision-making environment too complex for the development of a useable and useful DSS?

Integrated coastal management in the tropics requires the conservation of vulnerable and diverse ecosystems such as coral reefs and mangroves as well as the management of land and marine-based human activities. Decision-making for integrated coastal management involves multiple decision-makers and multiple stakeholders often with conflicting needs and interests. Decision support systems can be developed to improve our understanding of the inter-relationships between the natural and socio-economic variables and hence result in improved decision-making. The question is whether this decision making environment is actually too complex for the development of useful and useable decision support systems. This paper describes the components of the decision making environment and the components of a decision support system. It also explores the various techniques available to deal with different modelling needs, the constraints of inadequate data and the multi-objective decision making environment. In addition, different techniques of developing decision support systems can play important roles within integrated coastal management. Three coastal decision support systems are evaluated in terms of their design and role in integrated coastal management and are used to evaluate the potential to develop decision support systems for integrated coastal management.

Animals↗

PubMed2005

Developing effective prevention services for the real world: a prevention service development model.

A Prevention Service Development Model (PSDM) is presented as an approach to develop, prevention programs that are both effective and that are readily adopted for implementation in community settings. The model is an integration of concepts and methods from two fields, prevention research and marketing research as applied to new service development. Questions that are posed at each stage of the PSDM are described. Studies from the development of two preventive interventions are presented to illustrate research at several of the stages of the model.

Community Mental Health Services↗

PubMed2006

Transgenic mice expressing PAX3-FKHR have multiple defects in muscle development, including ectopic skeletal myogenesis in the developing neural tube.

The t(2;13) chromosomal translocation is found in the majority of human alveolar rhabdomyosarcomas (RMS). The resulting PAX3-FKHR fusion protein contains PAX3 DNA-binding domains fused to the potent transactivation domain of FKHR, suggesting that PAX3-FKHR functions to deregulate PAX3-specific target genes and signaling pathways. We previously developed transgenic mice expressing PAX3-FKHR under the control of mouse Pax3 regulatory sequences to test this hypothesis. We reported that PAX3-FKHR interferes with normal Pax3 developmental functions, with mice exhibiting neural tube and neural crest abnormalities that mimic those found in Pax3-deficient Splotch mice. Here we expanded those studies to show that developmental expression of PAX3-FKHR results in aberrant myogenesis in the developing somites and neural tube, leading to ectopic skeletal muscle formation in the mature spinal cord. Gene expression profiling indicated that PAX3-FKHR expression in the developing neural tube induces a myogenic pattern of gene expression at the expense of the normal neurogenic program. Somite defects in PAX3-FKHR transgenic animals resulted in skeletal malformations that included rib fusions and mis-attachments. As opposed to the neural tube defects, the severity of the rib phenotype was rescued by reducing Pax3 levels through mating with Splotch mice. Embryos from the transgenic line expressing the highest levels of PAX3-FKHR had severe neural tube defects, including exencephaly, and almost half of the embryos died between gestational ages E13.5-E15.5. Nearly all of the embryos that survived to term died after birth due to severe spina bifida, rather than the absence of a muscular diaphragm. These studies reveal a prominent role for PAX3-FKHR in disrupting Pax3 functions and in deregulating skeletal muscle development, suggesting that this fusion protein plays a critical role in the pathogenesis of alveolar RMS by influencing the commitment and differentiation of the myogenic cell lineage.

Animals↗

PubMed1990

Stimulation of myeloid colony development elaborated by colony forming cells--fibroblasts from rat developing ossicles.

Subcutaneous implantation of demineralized bone matrix in rats results in endochondral bone formation and bone-marrow development. The cascade of events leading to this process occurs following the accumulation of mesenchymal cells with colony forming cell fibroblasts (CFC-F) potential in the implanted area, a process which commences already 72 h post implantation. It is demonstrated herein that CFC-F from various stages of ossicle development (days, 3, 7, 10, 14 or 18) stimulate hemopoiesis to the same extent as judged by the number of granuloid-macrophage-progenitors (CFU-GM), developed as hemopoietic colonies, and by the ratio of granuloid to macrophagic colonies. High concentrations of CFC-F, however, tend to diminish the stimulatory capacity. Prostaglandin E, CFU-GM, CFC-F, ossicle, growth factors, microenvironment, hemopoiesis, development.

Animals↗

PubMed1996

Development of striatal dopaminergic function. III: Pre- and postnatal development of striatal and cortical mRNAs for the neurotrophin receptors trkBTK+ and trkC and their regulation by synaptic dopamine.

Known neurotrophins in the nigrostriatal system include brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) which exert biological effects after high affinity binding to their respective tyrosine kinase receptors, trkB and trkC. We measured striatal trkBTK+ and trkC mRNAs in rat brain sections with in situ hybridization histochemistry. Both trkBTK+ and trkC transcripts were present in the striatal anlage at embryonic day (E) 14 or 16. Striatal trkBTK+ mRNA levels increased to a peak in the late prenatal period and gradually declined in the postnatal period. In contrast, striatal trkC mRNA levels peaked on E16, then declined to fairly constant levels. Striatal trkBTK+ gene expression increased from the medial to lateral quadrants throughout development, whereas trkC mRNA increased from the lateral to medial quadrants prenatally but increased from the dorsal to ventral quadrants on postnatal days (P) 1 and 3. The distinct spatiotemporal developmental profiles of trkBTK+ and trkC mRNA suggest that their respective ligands BDNF and NT-4/5, and NT-3, may have specialized functions in striatal neuronal development. Because neurotransmitters may regulate neurotrophin function in developing neural systems, we treated rats of various ages with the indirect dopamine agonist cocaine and measured the effects of cocaine treatment on transcription of the trk genes. Acute 1 h cocaine treatment increased trkBTK+ and trkC mRNA levels in the P5 striatum but not in the E15, E20, or adult striatum. The trkBTK+ effect was blocked by pretreatment with the D1 receptor antagonist, SCH23390, and was not affected by pretreatment with the D2 receptor antagonist, eticlopride. In contrast, trkC regulation may be mediated by independent stimulation of D1 and D2 receptors. We hypothesize that the endogenous nigrostriatal neurotransmitter dopamine can modulate striatal neurotrophin responsiveness and thereby influence striatal neuronal development during a defined developmental period.

Animals↗

PubMed2005

Considerations for development of whole cell bacterial vaccines to prevent diarrheal diseases in children in developing countries.

Enteric pathogens constitute a major pediatric threat in the developing world through their impact on morbidity and mortality, physical and cognitive development and cause and effect relationship with malnutrition. Although many bacterial pathogens can cause diarrheal diseases, a group of less than 10 including Shigella spp., enterotoxigenic Escherichia coli (ETEC), Vibrio cholerae, and possibly, Campylobacter jejuni account for a significant percentage of these diseases in developing countries. Rotavirus is also a major cause of diarrheal diseases. Vaccines against these agents offer a potentially effective control measure against these diseases, but safe, practical, and effective vaccines for many of these agents have yet to be realized. Many vaccine development approaches are under investigation, but the one that is currently most advanced and that has been most widely applied to enteric pathogens is the use of orally administered live or killed whole pathogen preparations. If inactivated, these vaccines will probably be administered as multiple doses with approximately 10(10) to 10(11) total particles per dose, but they are relatively safe for oral administration. Further, they may not require a buffer for delivery and can be stored in liquid formulations. Fewer doses may be required for some live attenuated pathogen vaccines, but a buffer will most likely be required for oral delivery and the product must be stored in a dried formulation. Also, safety becomes more of a concern with live pathogens depending on the degree of attenuation, host immunocompetence, and the total number and kinds of attenuated pathogens which may be present in a combined agent vaccine. Both live and killed whole pathogen vaccines can be immunogenic and have the possibility to serve as vectors for other antigens. Although many organisms and serotypes are clinically important, by exploiting antigenic cross reactivity and using some pathogen components as vectors for cloned antigens of other pathogens, it could be possible to induce immunity against major enteric pathogens/serotypes with <10 whole pathogen components in a multi-agent vaccine. Safe and effective mucosal adjuvants may in the future be useful in whole pathogen vaccines, but they do not seem to be essential for immunization. Further, dietary supplements such as zinc, mixed routes of delivery and new regimens are under study which may in the future enhance further the effectiveness of the whole pathogen vaccines which now seem realizable in the near term. For this to happen, however, a coordinated and committed effort is necessary now to address the immunologic, regulatory, manufacturing, testing and implementation issues which will be involved in the realization of this important product to benefit children's health worldwide.

Bacterial Vaccines↗

PubMed1998

Cortical and cognitive development in 4th, 8th and 12th grade students. The contribution of speed of processing and executive functioning to cognitive development.

This study investigated cortical/cognitive relations in 30 4th, 8th and 12th grade students. All students were administered the Figural Intersection Test, a measure of cognitive development, and performed, three times with different targets, an event-related potential (ERP) oddball/selective-attention task. Two independent factors emerged from the ERP task that predicted development--speed of processing (P300 latency to Block 1 targets) and maturation of executive functioning (a composite ERP variable calculated as the ratio of RT and P300 latency divided by the accuracy to Block 2 targets). These two variables loaded on orthogonal factors in a principal components analysis, and were the only variables included in a stepwise regression of physiological variables on cognitive development. Speed of processing is modulated by myelination and synaptogenesis, and executive functioning is modulated by maturation of the frontal system. These electrophysiological markers could index these cortical transformations underlying cognitive development.

Adolescent↗

PubMed1991

A longitudinal study of the relationship between early language development and play development.

Temporal correspondences between the attainment of specific milestones in play and language were examined through a longitudinal study of four Japanese children (aged 0;7 to 0;11 at the beginning of the study). There were developmental correspondences between the onset of six language landmarks (the emergence of first words, naming words, vocabulary spurts, word-chains, nonproductive two-word utterances, productive two-word utterances) and the onset of subcategories of play. Language and play both reflected the development of underlying symbolic ability, and both developed in parallel manner at the single-word stage. After the emergence of word-chains, language and play developed interdependently. All the children proceeded through the same sequence of stages, but the rate of development was different depending on their environment.

Child, Preschool↗

PubMed1999

Ontogeny and regional variability of keratin 2e (K2e) in developing human fetal skin: a unique spatial and temporal pattern of keratin expression in development.

Keratin 2e (K2e) is expressed in the upper spinous and granular cells of adult epidermis. A highly specific polyclonal antibody was made against a C-terminal peptide of K2e and used to observe K2e expression at different developmental stages. At 12.5 weeks estimated gestational age (EGA) K2e was detected in trunk skin in scattered cells in the intermediate layer. At 13.5 weeks EGA, greater numbers of intermediate cells were stained with variable intensity, and staining in this pattern increased with age. Epidermal sheets from 14 weeks EGA showed that K2e + cells were excluded from developing hair follicles. At 135 days EGA, the following regional patterns were observed: in cheek, trunk, dorsal and ventral knee, elbow and dorsal hand there was moderate to intense staining of upper intermediate keratinocytes excluding cells of the hair canals and sweat ducts. The periumbilical region distinctly lacked K2e staining, while more distal areas showed increasing numbers of K2e + cells. The earliest expression of K2e was at 10 weeks EGA in the presumptive nail bed of developing digits. By 13.5 weeks EGA this pattern had shifted to the proximal nail fold, and K2e was absent in the nail bed. K2e was excluded from developing sweat glands and ducts and from developing hair follicles at the hair germ and early peg stages. By 15 weeks EGA in the fetal hair follicle small groups of cells were K2e + and by 19 weeks K2e + cells were seen at the level of the matrix. Some overlap in staining was detected for K2e with K10, and in palmar skin with K9; however, mostly the filamentous staining patterns for these keratins were distinctive. This study shows that the complex patterns of temporal and regional expression of K2e differ from known patterns for other epidermal keratins and suggest different regulation and function for this epidermal keratin.

Embryonic and Fetal Development↗

PubMedDate not supplied

The development of visuo-spatial working memory.

Children's performance on tests of visuo-spatial working memory improves with age, although relatively little is known about why this happens. One explanation concerns the development of the ability to recode visually presented information into phonological form. This process appears to be used from around 8 years of age and is a major contributor to tasks in which stimuli can be verbally labelled. However, evidence suggests that phonological recoding cannot account for all of the age-related change in performance on visuo-spatial working memory tasks. In this review, four other mechanisms (knowledge, processing strategies, processing speed, and attentional capacity) are considered in terms of their contribution to children's visuo-spatial working memory development.

Child↗

PubMed2001

Considerations for combination vaccine development and use in the developing world.

As more vaccines are developed and become available, combination vaccines will provide a way of delivering multiple antigens to avoid multiple injections and complications in the regular immunization schedules. The advantages of combination vaccines are that they decrease the discomfort of vaccine recipients and parents and also reduce the delivery cost of vaccines. We address some of the issues related to the use of combination vaccines in the developing world. Which vaccines are needed? Do developing countries have the appropriate infrastructure to deliver them? Can vaccines become affordable for countries with low incomes? And what is really needed to achieve the goal of providing developing countries with new vaccines of epidemiologic significance in a timely fashion?

Americas↗

PubMed1998

Sustaining the development of primary care in academic medicine. Working Group on Sustaining the Development of Academic Primary Care. Association of American Medical Colleges.

This article is the report of the Working Group on Sustaining the Development of Academic Primary Care, one of the six subgroups of the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) sponsored by the Association of American Medical Colleges (AAMC). To begin, the group draws a distinction between primary care and generalism. Primary care is a core domain of health care and, in the context of emerging integrated systems, will increasingly be a multidisciplinary shared function. Non-subspecialized physicians, or "generalists," are a key element in the provision of primary care, but do not act alone. Core competencies for primary care are central to the education of all physicians. Therefore, irrespective of workforce goals for generalist physicians, primary care should have a strong, central position in the medical school so that graduates can receive a sound general medical education and can be prepared for any specialty and for lifelong learning in an evolving health care system. For primary care to achieve that position, medical schools must integrate primary care into their missions, strategic plans, operation, organization, academic administrative structures, curriculum development, faculty development (both school- and community-based), resource development, alliances with appropriate clinical services networks, financial policy, and evaluation and educational monitoring systems. The group briefly describes the elements of those changes and also proposes ways that the AAMC and medical school leaders could promote the central role of primary care in medical schools.

Curriculum↗

PubMed1997

Developing elements of a learning organization in a metropolitan ambulance service: strategy, team development and continuous improvement.

First, presents a new model for developing a learning organization which is well within the grasp of today's organizations, since many of these already have the main components which provide the platform for this. Second, provides four measures of how an experiential workshop used to develop learning organization components may be evaluated. Despite huge international popularity for experiential workshops, effectiveness measurements are rarely used. Third, presents a case study of how to begin developing a learning organization through developing middle management in a metropolitan ambulance service.

Ambulances↗

PubMed1983

Development of the pre-school child: the validation of a psychomotor screen, and the influence of the home environment on psychomotor development.

The present study was designed to validate and standardize a short psychomotor screening test on Australian four-year-old-preschool children and to assess their home environment using Caldwell's HOME Inventory. The Adelaide Psychomotor Screen (APS) is a short, 10-15 minute screening test which uses 13 separate items to assess "General" development, "Gross Motor" development, "Social/Emotional Behaviour" and "Speech". In the area of "General" development, 12 children screened as "abnormal" and 54 children screened as "normal" were further assessed by a psychologist on the McCarthy Scales of Children's Abilities. There was a high correlation between the APS "General" scores and the McCarthy (General Cognitive Index) scores (r = 0.75, p less than 0.001 for the younger children, and r = 0,90, p less than 0.001 for the older children). Caldwell's HOME Inventory takes an hour to complete, and involves a visit by the assessor to each home. The correlation between the HOME total scores and the McCarthy (General Cognitive Index) scores was r = 0.06, p less than 0.001. It is suggested that the HOME Inventory may be more valuable as a predictor of a child's future development than an index of his present developmental status. It is suggested that nurses and teachers used the APS as a screening test of the individual child, and use the HOME inventory as an assessment of the home environment.

Analysis of Variance↗

PubMed1996

Expression of bone marrow stromal cell specific antigen during murine development: its expression in embryonic hematopoietic tissues as well as in other developing tissues.

Monoclonal antibody R4-A9 demonstrated specificity for a cell surface antigen of stromal cells in murine bone marrow and spleen. In order to identify patterns of expression that may elucidate the potential role of R4-A9 antigen, the developmental expression of this antigen in mouse embryos from 8 days post-coitum to 5 days post-partum was investigated by immunohistochemistry. At an early developmental stage, weak staining for R4-A9 antigen could be detected in the yolk sac. At later stages, strong staining of this antigen was detected predominantly in the embryonic liver, the main site of embryonic hematopoiesis. However, concomitant with the decreased staining in the liver, increased expression of this antigen was observed in bone marrow and spleen. Therefore, the changes in expression in those hematopoietic tissues suggest that its expression is coordinately regulated during the developmental stage of the sites of embryonic hematopoiesis. Compared with the distribution of R4-A9 antigen in adult tissues as previously reported, the expression of this antigen in fetal tissues was more widespread during the period of organogenesis, and was most abundant in other developing tissues, including the heart, skin, and lung. In contrast, fetal expression detected in hematopoietic and other developing tissues was lost after birth. These results taken together show a marked gradient of R4-A9 antigen expression, with the highest level at the peak of organ development, raising the possibility that this molecule may act as a growth/differentiation factor both in hematopoietic and other developing tissues in a fetus.

ADP-ribosyl Cyclase↗