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An attempt was undertaken to generalize and interpret the data on thermal-temporal patterns of development of the poikilothermic animals obtained using relative criteria of development duration.
The quantitative relationship between environmental degradation (pollution) and the factors that influence it can be expressed by the identity: Pollution = population x (good/population) x (pollution/good), where "affluence" is expressed as good/population and the technology of production as pollution/good. Annual data for the emission of carbon monoxide and nitrogen oxides from mobile sources and for the use of pesticides and inorganic nitrogen fertilizer from agriculture, for the member countries of the Organization for Economic Cooperation and Development and the United States, were analyzed to determine the relative change in the three factors over the period 1970-1987. In each case the considerable variation in pollutant emissions among the different countries is most closely related to the concomitant change in the technology factor (pollution/good). In contrast, there is much less variation among the countries in the population and "affluence" factors, which are consequently uncorrelated with the variation in pollutant emissions. The data show that the change in production technology is by far the most important of the several factors responsible for changes in pollution emission.
Community-based programmes for prevention and control of cardiovascular diseases (CVD) started in Europe and the USA in the early 1970s. High mortality from CVD in Finland led to the start of the North Karelia Project. Since then, a vast amount of scientific literature has accumulated to present results and discuss experience. The results indicate that heart health programmes have a high degree of generalizability, are cost-effective and can influence health policy. In the 1980s the focus of programmes expanded from CVD to noncommunicable diseases (NCD), mainly because of the common risk factors. Attention has now turned to promoting this approach in developing countries, where the prevalence of NCD is growing. Theory and experience show that community-based NCD programmes should be planned, run and evaluated according to clear principles and rules, collaborate with all sectors of the community, and maintain close contact with the national authorities. In view of the burden of disease they represent and of globalization, there is a great need for international collaboration. Practical networks with common guidelines but adaptable to local cultures in a flexible way have proved to be very useful.
OBJECTIVE: To examine the long-term effects of the Seattle Social Development Project intervention in promoting positive adult functioning and preventing mental health problems, crime, and substance use (including tobacco, alcohol, and other drugs) at 21 years of age. DESIGN: This nonrandomized controlled trial followed up participants to 21 years of age, 9 years after the intervention ended. We compared the following 3 intervention conditions: a full 6-year intervention (grades 1 through 6); a late 2-year intervention (grades 5 and 6 only); and a no-treatment control condition. SETTING: Eighteen public elementary schools serving diverse neighborhoods, including high-crime neighborhoods, of Seattle, Wash. PARTICIPANTS: A sex-balanced, multiethnic sample of 605 participants across the 3 conditions who completed interviews at 21 years of age (94% of the original sample in these conditions). INTERVENTIONS: Teacher training in classroom instruction and management, child social and emotional skill development, and parent training. MAIN OUTCOME MEASURES: Self-reports of functioning in school and work, emotional and mental health, and crime and substance use at 21 years of age and official court records. RESULTS: Broad significant effects on functioning in school and work and on emotional and mental health were found. Fewer significant effects on crime and substance use were found at 21 years of age. Most outcomes had a consistent dose effect, with the strongest effects in subjects in the full-intervention group and effects in the late-intervention group between those in the full-intervention and control groups. CONCLUSIONS: A theory-guided preventive intervention that strengthened teaching and parenting practices and taught children interpersonal skills during the elementary grades had wide-ranging beneficial effects on functioning in early adulthood.
Glial cell line-derived neurotrophic factor (GDNF) has potent trophic action on fetal dopaminergic neurons. We have used a double immunocytochemical approach with antibodies that recognize GDNF and tyroxine hydroxylase (TH) or the phosphoprotein DARPP-32, to study the developmental pattern of their interactions in the rat striatum and in intrastriatal striatal transplants. Postnatally, at one day and also at 1 week, GDNF showed a patchy distribution in the striatum, together with a high level of expression in the lateral striatal border, similar to that observed for the striatal marker DARPP-32 and also for TH. In the adult striatum, there was diffuse, weak immunopositivity for GDNF, together with widespread expression of DARPP-32-positive neurons and TH-immunoreactive (TH-ir) fibers. In 1-week-old intrastriatal striatal transplants, there were some GDNF immunopositive patches within the grafts and although there was not an abundance of TH-positive fibers, the ones that were seen were located in GDNF-positive areas. This was clearly evident in 2-week-old transplants, where TH-ir fibers appeared selectively concentrated in GDNF-positive patches. This pattern was repeated in 3-week-old grafts. In co-transplants of mesencephalic and striatal fetal tissue (in a proportion of 1:4), TH-ir somata were located mainly at the borders of areas that were more strongly immunostained for GDNF, and TH-ir fibers were also abundant in these areas and were found in smaller numbers in regions that were weakly positive for GDNF. These results demonstrate that GDNF-ir is coincident with that for TH and DARPP-32, and suggest that GDNF release by fetal striatal neurons both in normal development and in developing striatal grafts may have not only a trophic but also a tropic influence on TH-ir fibers and may be one of the factors that regulate dopaminergic innervation of the striatum.
The transcription factor FKHL7 gene has recently been associated with the anterior segment dysgenesis disorder of the eye known as Axenfeld-Rieger anomaly (ARA). A growing body of evidence indicates that mutations in FKHL7 cause not only defects in the anterior segment of the eye but defects in the heart valves and septa as well. In order to evaluate its contribution to normal heart septation and valve formation, expression of the mouse homologue Mf1 in embryonic hearts was analyzed by in situ hybridization. A weak but significant level of Mf1 expression could be detected in the endocardium of mouse embryos as early as day 8.5 post-conception (p.c.). Mf1 expression was undetectable in the hearts of day 9.5 p.c. embryos, but by day 10.5-11 p.c., Mf1 transcripts could be found again in the endocardium of both the atrium and ventricle and a relatively strong signal was observed in the dorsal portion of the septum primum, in what appeared to be the spinal vestibule. At day 13 p.c. when aortic and pulmonary trunks are separated, relatively more Mf1 transcripts were detected in the leaflets of aortic, pulmonary, and venous valves, the ventral portion of the septum primum, as well as in the single layer of cells on the edges of the atrioventricular cushion tissues. Surprisingly, there was no signal detected in the developing interventricular septum. At day 15 p.c., overall Mf1 signals were greatly decreased. However, significant levels of expression could still be observed in the atrial septum, the tricuspid valve, the mitral valve, and in the venous valve but not in the interventricular septum. The temporal and spatial expression patterns of the Mf1 gene in developing mouse hearts suggest that Mf1 may play a critical role in the formation of valves and septa with the exception of the interventricular septum. This is further supported by our studies showing that mutations in the FKHL7 gene were associated with defects in the anterior segment of the eye as well as atrial septal defects or mitral valve defects. Dev Dyn 1999;216:16-27.
We examined the effect of consumption of graded increases of dietary fiber (soft white wheat bran) on the development of mammary gland carcinomas in intact female Sprague-Dawley rats during the promotion stage of carcinogenesis, induced with 7,12-dimethylbenz(a)anthracene (DMBA). The percent of rats with mammary carcinomas, the total number of mammary carcinomas and the mean number of mammary carcinomas per rat were reduced significantly at all fiber levels examined compared to rats fed a control diet. Inclusion of 9.6% fiber in the diets of ovariectomized rats that had been treated with a single i.v. dose of 2.5 mg DMBA/100 g body weight 2 weeks prior to removal of the ovaries resulted in a significant decrease of carcinomatous and benign mammary tumors compared to ovariectomized rats fed a control diet. Development of spontaneous mammary carcinomas in virgin C3H/HeOuJ female mice and growth of a transplantable mammary gland tumor in such mice were reduced by inclusion of 9.6% fiber in the diet, a reduction that was significant or just barely missed significance, depending on the source of the fiber. Our observations provide evidence that inclusion of soft white wheat bran in the diet is effective in the suppression of mammary gland tumorigenesis in an array of experimental animal models.
The development of the vasculature of the pars distalis of two strains of rat, Fischer 344 (F344) and Lewis (LEW), was followed in 16-day (16d) and 20-day (20d) fetuses, and in 1-day (1d), 5d, 20d, 50d, and 6-month-old females. No differences in the two strains were apparent in 16d fetuses; and the capillaries that were present were immature, i.e., tall, non-fenestrated endothelial cells, and were surrounded by poorly delineated pericapillary spaces. Immature capillaries also were predominant in 20d fetuses of both strains. Agranular folliculo-stellate cells were identifiable, projecting endfeet to the parenchymal basal lamina in 20d F344 fetuses, but not in LEW fetuses. Postnatally, the capillaries of LEW rats became progressively more thin-walled and fenestrated, and were surrounded by a pericapillary space that was well delimited by basal laminae at 20d. In 50d and 6-month LEW rats, capillaries were intact and surrounded by well-defined pericapillary spaces. By comparison in F344 rats, the capillaries remained more immature even in 50d rats and older. In addition, in F344 rats focal disruptions in endothelial cells and disruptions in parenchymal and capillary basal laminae were present in all postnatal stages, and a dramatic accumulation of plasma was evident within the pericapillary spaces at 20d. Endfeet processes of folliculo-stellate cells were abundant at the parenchymal basal lamina of 1d and 5d F344 neonates, but only rarely were identified in LEW neonates. Some activation of folliculo-stellate cells, i.e., increased numbers of lysosomes and dilated endoplasmic reticulum, was present in 50d F344 rats. Connective-tissue cells within the pericapillary space also were numerous and activated in F344 rats. Discrete gaps in the parenchymal basal lamina were evident subjacent to the folliculo-stellate cell endfeet in F344 rats but not in LEW rats. The vascular bed of F344 rats differs in its development from that of LEW rats. Characteristic of the F344 strain is a persistence of more immature capillaries, an inherent vascular fragility, and an activated state of folliculo-stellate cells.
BACKGROUND: The problem of how the functional compartments of the Golgi apparatus organizes during cell differentiation to become a well-formed Golgi apparatus is as yet an unresolved issue. This study was designed to define the involvement of the trans-Golgi network (TGN) and the Golgi stack in organizing the Golgi apparatus. METHODS: The distribution of the TGN marker enzyme was examined in the ameloblast of developing rat molar tooth germs using cytochemistry with Co-enzyme A phosphatase (CoA Pase) and cytidine monophosphatase (CMPase). RESULTS: Typically formed Golgi apparatus was observed in the secretory ameloblast but not in the presecretory ameloblast. Organization of the Golgi apparatus through the presecretory ameloblast was noted. In the presecretory ameloblast, Golgi stacks of different sizes and clusters of small vesicles were located in the cytoplasm lateral to the nucleus. The saccules with enzymes marked for TGN were also observed in the cytoplasm lateral to the nucleus. These saccules were adjacent to the cluster of small vesicles and/or the Golgi stack. Upon cell differentiation, Golgi stacks were seen in line along the long axis of the cell, and the file of the stacks in the cytoplasm lateral to the nucleus was formed. The positive saccule was seen in a parallel line equal to the length of the Golgi stacks. CONCLUSIONS: In organizing the Golgi apparatus, the development process of the TGN and the Golgi stack appear to be different, and new Golgi stacks seem to be formed through the accumulation of small vesicles near the pre-existing TGN.
The development and organization of Purkinje cell axons and their collaterals was studied in the bullfrog using the Golgi-Kopsch method. In the tadpole, axonal collaterals are few and usually unbranched. In the adult, however, intracortical axonal collaterals of Purkinje cells are more numerous, and they form a meager supraganglionic plexus and a more extensive infraganglionic plexus. In contrast to the pattern seen in higher vertebrates, these plexuses have a tendency to be distributed along the length of the cerebellar plate in both tadpoles and froglets. In addition, collateral branches that form intracortical plexuses apparently increase throughout the course of cerebellar development in this species.
The existing table of stages of the normal development of the axolotl (Ambystoma mexicanum) ends just after hatching. At this time, the forelimbs are small buds. In this study, we extend the staging series through completion of development of the forelimbs and hindlimbs.
7-dehydrocholesterol reductase (7-Dhcr) catalyses the final step in the pathway of cholesterol biosynthesis. Human patients with inborn errors of 7-Dhcr (Smith-Lemli-Opitz-Syndrome) have elevated serum levels of 7-dehydrocholesterol but low levels of cholesterol, which in phenotypical terms can result in growth retardation, craniofacial abnormalities including cleft palate, and reduced metal abilities. This study reports the isolation and molecular characterisation of 7-dehydrocholesterol reductase (Xdhcr7) from Xenopus laevis. During early embryonic development, the expression of Xdhcr7 is first of all spatially restricted to the Spemann's organizer and later to the notochord. In both tissues, Xdhcr7 is coexpressed with Sonic hedgehog (Shh), which itself is cholesterol-modified during autoproteolytic cleavage. Data from Xdhcr7 overexpression and knockdown experiments reveals that a tight control of cholesterol synthesis is particularly important for proper development of the central and peripheral nervous system.
Pronucleus transplanted mice have been produced, but their donor male pronuclei were derived from mature sperm and were completely synchronous with female pronuclei because both male and female pronuclei came from the same fertilized oocyte. The present study firstly produced male pronuclei by introducing round spermatids into enucleated mouse oocytes, then transferred the male pronuclei into mouse oocytes at three activation stages and finally compared the effect of three kinds of oocytes on the development of reconstructed embryos. Our results indicate that, in enucleated oocytes, mouse round spermatid nuclei can transform to male pronuclei in a higher proportion, and the synchronization between male and female pronucleus does not significantly influence the early cleavage but the later and full-term development of reconstructed embryos.
The volatile anesthetic halothane, when present at fertilization, dose-dependently increases the incidence of abnormally developing sea urchin embryos at the first cell division. Microscopic examinations of eggs stained with aceto-orcein or the DNA fluorochrome bisbenzimide and direct observations on isolated sperm aster complexes show that halothane induces polyspermy (multiple sperm entry) when present at fertilization. Experimental evidence suggests that anesthetic-induced polyspermy involves impairment of both the fast (electrically mediated) and slow (morphological) blocks to multiple sperm entry. These observations clearly show that relatively brief exposures to halothane at fertilization cause polyspermy and that this effect is almost certainly responsible for the ensuing abnormal development observed at the first cell division.
OBJECTIVE: We investigate a knowledge-based help system for developers of an integrated clinical information system (CIS). The first objective in the study was to determine the system's ability to answer users' questions effectively. User performance and behavior were studied. The second objective was to evaluate the effect of using questions and answers to augment or replace traditional program documentation. DESIGN: A comparative study of user and system effectiveness using a collection of 47 veritable questions regarding the CIS, solicited from various CIS developers, is conducted. Most questions were concerning the clinical data model and acquiring the data. MEASUREMENTS: Answers using current documentation known by users were compared to answers found using the help system. Answers existing within traditional documentation were compared to answers existing within question-answer exchanges (Q-A's). RESULTS: The support system augmented 39% of users' answers to test questions. Though the Q-A's were less than 5% of the total documentation collected, these files contained answers to nearly 50% of the questions in the test group. The rest of the documentation contained about 75% of the answers. CONCLUSIONS: A knowledge-based help system built by collecting questions and answers can be a viable alternative to large documentation files, providing the questions and answers can be collected effectively.
During the past few years important advances have been realized in the understanding of the molecular and cellular mechanisms operating in the differentiation of Schwann cells from neural crest cells. In particular the development of in vitro culture systems has allowed the analysis of commitment to the Schwann cell lineage, identification of an intermediate between the neural crest cell and the Schwann cell, and initial analysis of the factors controlling determination and differentiation processes. These studies point in particular to major roles for neuregulins which appear to be involved in the control of cell survival, proliferation, and differentiation, as well as of gene expression at different levels of the pathway.
During the early stages of development various cell adhesion molecules (CAMs) and fibroblast growth factor receptors (FGFR) are expressed throughout the retinal neuroepithelium. The ability of retinal ganglion cells to project their axons to the optic fissure depends, in part, on cell-cell interactions mediated by cell adhesion molecules. In the present study we show that the ability of the firstborn rat retinal ganglion cells to extend axons in vitro can be stimulated by NCAM and L1, but not N-cadherin. Both CAM responses can be fully inhibited by antibodies that block neuronal fibroblast growth factor receptor function and by agents that block defined steps in the FGFR signal transduction cascade. When added to living E13.5 rat retinal whole-mount preparations the same agents induced errors in the orderly establishment of young axon patterns in the retinal periphery and caused axons in the retinal center to defasciculate. These results suggest that the activation of the fibroblast growth factor receptor signal cascade not only promotes survival and proliferation of various cell types but can also mediate intraretinal axon guidance.
In the developing chicken cerebellar cortex, three cadherins (Cad6B, Cad7, and R-cadherin) are expressed in distinct parasagittal segments that are separated from each other by ribbons of migrating interneurons and granule cells which express R-cadherin and Cad7, respectively. The segment/ribbon pattern is respected by the expression of other types of molecules, such as engrailed-2 and SC1/BEN/DM-GRASP. The cadherin-defined segments contain young Purkinje cells which are connected to underlying nuclear zones expressing the same cadherin, thereby forming parasagittal cortico-nuclear zones of topographically organized connections. In addition, R-cadherin-positive mossy fiber terminals display a periodic pattern in the internal granular layer. In this layer, Cad7 and R-cadherin are associated with synaptic complexes. These results suggest that cadherins play a pivotal role in the formation of functional cerebellar architecture by providing a three-dimensional scaffold of adhesive information.