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Development of the lateral line system in Xenopus laevis. I. Normal development and cell movement in the supraorbital system.

During development of Xenopus laevis, the supraorbital lateral line system (i.e. the parietal and supraorbital lines of organs and the anterior auditory group of organs) is all derived from a single primordium located in the ear region of the epidermis. The primordium elongates first by active movement along the dorsal margin of the eye. Individual primary organs are then formed by progressive fragmentation of the streak-like primordium. After fragmentation, passive displacement of the organs due to skin growth seems to play the main role in altering the arrangement of the line system. Transplantation experiments confirmed that non-placodal epidermal cells are not incorporated into the developing system. The active elongation of the primordium is due to cell multiplication, and not due to cell rearrangement or change in cell shape or size. Cell multiplication is not confined to a growth zone, but dividing cells are randomly distributed throughout the primordium. All cells of a primordium have to change position during its elongation.

Animals↗

An electron microscopic study of the development of axons and dendrites by hippocampal neurons in culture. I. Cells which develop without intercellular contacts.

We have studied the processes which are elaborated by hippocampal neurons in dissociated cell culture. Nerve cells, which were obtained from fetal rats at 18 to 20 days of gestation, were plated at very low density onto polylysine-treated coverslips and were maintained in serum-free medium. Under such conditions, some cells develop without contacting any neighboring neurons or glial cells. Examples of such isolated cells which had developed for 1 week in culture were studied first by light microscopy, then they were sectioned parallel to the substratum so that all portions of the cell and its processes could be examined by electron microscopy. Dendrites and axons could be clearly distinguished by both light and electron microscopy. Dendrites were rather thick at the base but tapered rapidly to a minimum diameter of about 0.5 micron and contained polyribosomes throughout their length. Axons, which were several times longer than the dendrites, were thinner at the origin, tapered much less, and were essentially ribosome-free. These ultrastructural differences were particularly obvious at branch points, where cytoplasmic organelles tend to accumulate. Clusters of polyribosomes were invariably present at dendritic branch points, but they were never observed at axonal branch points. The axons most commonly arose from the proximal portion of a dendrite rather than directly from the cell body as they typically do in situ. These observations show that the fundamental differences in form and in the distribution of ribosomes between axons and dendrites can be established in cell culture. Contact with afferent fibers or with target cells during the period of process outgrowth is unnecessary for the expression of these features of axonal and dendritic differentiation.

Animals↗

[Neuroradiology of embryonal brain development. Comparative studies on the prenatal development of brain vessels and liquor spaces in mammals and humans].

In more than 400 mammalian and human embryos and fetuses of an age of gestation of 4 weeks up to term, the prenatal development of the cerebral vessels and ventricles was studied by radiological techniques. Postmortal arterio- and phlebographies demonstrated the complex transformations of the leptomeningeal arteries and veins. The capillary growth within the brain itself was examined by a combination of microangiographic and histological techniques, and a clear morphological correlation between the differentiation of the nervous tissue and the invasion of the capillaries was shown. By ventriculography, the changes of the size and shape of the ventricular system were documented, and quantitative development diagrams of the cerebral ventricles could be established. On the basis of these morphological findings, in vivo, angiographies were carried out in fetal cats (in utero) and also in chicken embryos of an age of gestation of 5--14 days. It could be shown, that the average circulatory speed of the blood stream within the carotid arteries increases parallel to the enlargement of the embryo and its arteries, whereas the circulatory time and the number of heart beats during the period of carotid opacification does not change to a great extent.

Angiography↗

Embryonic development of the hirudinid leech Hirudo medicinalis: structure, development and segmentation of the germinal plate.

The germinal plate of 5- to 12-day-old embryos of the leech Hirudo medicinalis consists of an anterior and a posterior sector that differ both structurally and developmentally. The posterior sector includes the five pairs of teloblasts and five paired longitudinal bandlets of stem cells and their descendant blast cells. The mesoteloblast pair and their descendant cells of the m bandlet divide spirally and give rise to bilaterally paired cell clusters. The four ectoteloblast pairs and their descendant cells of the n, o, p and q bandlet pairs divide unidirectionally and give rise to paired one-cell-thick and four-cell-wide ectodermal arches. The developmentally more advanced anterior sector of the germinal plate consists of differentiating ectodermal and mesodermal cells engaged in organogenesis. The mesodermal cell clusters develop into somites, whereas the expanding ectodermal arches develop into nerve cord ganglia and epidermis. Rostrocaudal expansion of somite tissue results in the formation of obliquely oriented intersegmental septa, causing the ganglia to take on an intersegmental distribution. The first sign that formation of body segments has been completed is the appearance of a bilateral gap in the mesodermal bandlet of the posterior sector of the germinal plate. This gap seems to trigger degeneration of the posterior sector of the germinal plate.

Animals↗

[The larval development of Dipetalonema rugosicauda (syn. Wehrdikmansia rugosicauda) in the tick Ixodes ricinus. II. The development of Dipetalonema rugosicauda in Ixodes ricinus and investigations about the occurrence of the microfilariae in the roe deer (C. capreolus) (author's transl)].

Microfilariae of D. rugosicauda, which were taken up by nymphs of I. ricinus during their attachment on roe deers, developed in those ticks to infective larvae after two moults. The larval development lasted 56-67 days at 20-22 degrees C and occurred similar to other species of Dipetalonema inclusive a sausage stage. During this time the nymphs moulted to adult ticks. Adult females and males of I. ricinus collected in the area of Biberach/Riss, Southern-Germany, contained up to 12 infective larvae of D. rugosicauda per tick. The occurrence of those infective larvae and of microfilariae in roe deers depended on the season. The highest rate of infected ticks was 4.3% in spring, whereas the maximum rate of infected roe deers was 46.8% in autumn. Based on investigations of fawns of roe deers the prepatent period of D. rugosicauda can be estimated as approximately 6 months. Compared with microfilariae of Onchocerca tarsicola from red deers the microfilariae of D. rugosicauda prefered deeper layers of the ear skin of their hosts. Besides D. rugosicauda microfilariae of a further hitherto unknown species were detected in the ear skin of roe deers additionally. They resembled microfilariae of O. tarsicola.

Animals↗

[Branchial arch development in the rat and mouse. I. Development of the sinus cervicalis and operculum].

The development of the branchial arch region was studied in mouse embryos at the age of 10-13 days after conception [end of embryonal day (ED) 10 to end of ED 13] and in rat embryos at the age oa 1-14 days after conception (end of ED 11 to nd of ED 14) using SEM and serial semithin sections. Special attention was paid to the development of the cervical sinus and the branchial operculum. In both rodents, a typical operculum was not found. Instead, the caudal branchial arch region was remodeled by a rapid growth of the second branchial arch, the retrobranchial ridge and the epipericardial ridge, thus forming a progressively deeper grove in this region, the sinus cervicalis. The epithelium of the fourth and sixth branchial arches participated in the formation of the vagus placode, which in later stages was depressed into a grove dorsally and lost its connection with the surface. Finally, the second branchial arch and the cardiac bulge fused compressing the third branchial arch, the second and third branchial grooves and the aperture of the vagus placode. A typical vesicula cervicalis, lined by ectodermal epithelium and collecting the second, third and fourth branchial grooves and the glossopharyngeal and vagus placodes, was not found. However, single or multiple slit-like lumina may persist within the epithelial remnants of the second and third branchial grooves and the vagus placode.

Animals↗

Autonomous development of parts isolated from primitive-streak-stage mouse embryos. Is development clonal?

The relationship between growth rate and regionalization of amphibian, bird and mammalian embryos is briefly reviewed. In contrast to the others, mammals start gastrulation with few cells but accelerate cell proliferation coincidentally. Experiments are described which demonstrate (1) autonomous development of pieces isolated surgically from such mouse embryos, and (2) an absence of regeneration or regulation. Since such embryos regulate completely after chemically induced random cell death it is postulated that these results reflect developmental determination and a resulting mosaicism that suggests development may have a clonal basis. Maps are drawn, allocating positions to various tissues in the embryo.

Allantois↗

[The development of the adrenal cortex in pig (Sus scrofa domestica). (A contribution on the development of the fetal interior zone of the adrenal cortex in pig) (author's transl)].

The adrenals of pigs have been investigated histologically and histochemically during different periods of time pre- and postnatally. The pig (Sus scrofa domestica) shows a proper fetal cortex in the prenatal development of the adrenal gland. This involves slowly during the last quarter of pregnancy. A weight reduction is not noted thereby. Just before delivery the adrenal cortex of the pig has been subdivided into a zona arcuata and zona fasciculata. The zona reticularis develops only postnatally.

Adrenal Cortex↗

Re-engineering drug development: integrating pharmacoeconomic research into the drug development process.

Pharmacoeconomic research will be an increasingly important aspect of drug development as providers, third-party payers, and worldwide government health agencies use cost-effectiveness and quality-of-life data to assist in making decisions on optimal pharmaceutical treatment protocols, formulary listings, and reimbursement. It is in the best interest of pharmaceutical companies to have an established, well-integrated pharmacoeconomic research program that can respond to the dynamic health-care environment and proactively plan a program to optimize patient care. The new paradigm for pharmacoeconomic research will require establishment and successful management of many internal and external customer relationships. This article discusses one company's organization of these relationships and how they are integrated into the drug development process during each stage of the product life cycle.

Drug Evaluation↗

[Directions in the development of postsynaptic nondepolarizing muscle relaxants with rapidly developing action].

The experiments on unconscious cats have shown that the myoparalytic effect of postsynaptic non-depolarizing myorelaxants which have a trimethylammonium cationic group develops more rapidly than that of their triethylammonium analogues. The compound IEM-1213 is given as an example of a trimethylammonium derivative with the rigid structure of the molecule having an unusual rapidly developed effect.

Action Potentials↗

Ascorbic acid delays the development of tolerance to amphetamine induced anorexia but does not affect the reverse tolerance which develops to the locomotor activity.

Ascorbic acid (1 g/kg) accentuated anorectic and locomotor effects of amphetamine (5 mg/kg) and delayed development of tolerance to anorectic effect. On the contrary, it did not alter the pattern of reverse tolerance to increased locomotor activity. The results suggest that modulation of dopamine receptor sensitivity by ascorbic acid may be the reason for the delay in development of tolerance to amphetamine induced anorexia.

Amphetamine↗

Development of computer-directed methods for the identification of hyperactivated motion using motion patterns developed by rabbit sperm during incubation under capacitation conditions.

Rabbit spermatozoa developed motions that mimicked hyperactivated motility during incubation for 16-20 hours under capacitation conditions and in several other commonly used media. Sperm from some rabbits failed to acquire this type of motility, and sperm from others failed to survive the long incubation time. Four motility patterns developed during incubation for 16-20 hours. Motility parameters measured by the CellSoft and CellTrak motion analysis systems were similar except for the average amplitude of lateral head displacement. Multivariate discriminant analysis with complementary regression analysis, and an unrelated tree structured classification method (CART), were used to derive rules, based on motility parameters, for the objective classification of sperm into the two motility classes: 1) nonhyperactivated motility and 2) hyperactivated motility or motility that mimicked hyperactivated motility. The motility parameter wobble (WOB) as superior to the commonly used parameter, linearity, as a classifier of motility types. It classified sperm into the two motility groups with 96.6% efficiency and, together with curvilinear velocity (VCL), attained classification efficiencies of 98%. The classification model produced by CART was preferred over the one obtained by discriminant analysis. The rule for motility classification was dependent on the motion analysis system used to measure the motion parameters. The rule for the CellSoft system, WOB < or = 0.78 and VCL > or = 51 microns/second, classified sperm with an efficiency of 98%, whereas the rule for the CellTrak system, WOB < or = 0.6 and VCL > or = 55 microns/second, achieved a classification efficiency of 97%. These rules should facilitate the study of sperm hyperactivation and its role in sperm function.

Animals↗

[Concept development in theory development].

A concept development is the first part of the theory development. Concepts are linked together and form hierarchical, compositional, functional and heterogenous concept systems. In illustrating concept systems, diagrams, tables and figures are used. Concept systems are maps to help nurses, teachers and managers in examining the interests of nursing science in detail, to understand more profound way, and to produce still more new aspects for the interest.

Concept Formation↗

Expression of FosB during mouse development: normal development of FosB knockout mice.

FosB, one of the members of the Fos family, is rapidly induced in many cell types upon stimulation and has a stimulatory effect on the proliferation of cultured cells. To understand the tissue distribution of FosB, we have studied its expression pattern by immunohistochemistry in newborn and late embryonic stage mice. These results show that FosB is widely expressed with the highest levels of expression observed in both bony and cartilagenous regions of developing bone. FosB is also detected within whisker follicles, liver, and epidermal tissue. To study the role of FosB in mammalian development we generated embryonic stem (ES) cells, mice and mouse embryo fibroblasts (MEFs) that are deficient for FosB. FosB -/- mice are born at a normal frequency, are fertile and present no obvious phenotypic or histologic abnormalities. FosB-deficient ES cells and MEFs proliferate and enter the S phase normally and we do not find upregulation of other fos family genes to compensate for the lack of FosB. However, we do find that the induction of two AP-1 containing genes is reduced after stimulation of FosB-deficient cells, demonstrating that FosB does indeed play a functional role in transcriptional regulation.

Animals↗

Dementia drug development: use of information systems to harmonize global drug development.

Dementia is a worldwide problem with regional differences in distribution. In North America and Western Europe, it is estimated that approximately 70 percent of all cases of dementia are caused by Alzheimer's disease (AD) and 15 percent by vascular dementia. Infectious and metabolic causes of chronic cognitive impairment are more common than AD in developing countries, but as the populations of these countries continue to age rapidly, the problem of age-related dementias such as AD will become enormous. Around the world, numerous medications have been approved for the treatment of dementia, although relatively few have been approved specifically for AD. In Japan, for example, over 20 medications have been approved, primarily for the treatment of vascular dementia, but they are also used for other dementias. Most of these drugs would not meet current standards for efficacy (i.e., Food and Drug Administration or European Union proposed guidelines, or de facto standards set by the approval of tacrine), although most are safe. Similarly, in Europe there are wide variations in available drugs, and many might not be approved if introduced today. This article discusses the International Working Group for the Harmonization of Dementia Drug Guidelines, a collaborative effort to develop safe, effective treatments for dementia by promoting harmonization of regulatory guidelines and multisite, multinational studies to produce global dossiers. It focuses on the use of information systems to achieve this goal.

Dementia↗

Practice parameter for the use of red blood cell transfusions: developed by the Red Blood Cell Administration Practice Guideline Development Task Force of the College of American Pathologists.

A practice parameter has been developed to assist physicians in the therapeutic use of red blood cell transfusions. The developers of this parameter used the best available information from the medical literature, as well as clinical experience and the extensive reality testing required by the College of American Pathologists for approval. In acute anemia, a fall in hemoglobin values below 6 g/dL or a rapid blood volume loss of more than 30% to 40% requires red blood cell transfusions in most patients. However, tissue oxygenation provides a better indication of physiologic need in situations where invasive monitoring provides this information. When these data are not available, heart rate and blood pressure measurements and the nature of bleeding (active, controlled, uncontrolled) supplement the hemoglobin value in guiding the transfusion decision. In sickle cell disease and thalassemias, red blood cells are transfused to prevent acute or chronic complications. Red blood cell transfusions are used in chronic anemias unresponsive to pharmacologic agents based on the patient's symptoms. Guidelines must be altered for neonates who require an increase in hematocrit to above 0.30 to 0.35 when respiratory distress is present. Indications for red blood cell transfusion for the pregnant or postpartum patient are similar to those for the nonpregnant patient. Risks of transfusion, particularly transmissible disease and incompatibility, remain but have been reduced. Thus, red blood cell transfusion continues to be a powerful therapeutic tool when used judiciously and carries less risk than in the recent past.

Adult↗

Augmentation of serotonin in the developing superior colliculus alters the normal development of the uncrossed retinotectal projection.

A previous study from this laboratory showed that sprouting of serotoninergic axons in the hamster's superior colliculus (SC) induced by a single subcutaneous injection of 5,7-dihydroxytryptamine (5,7-DHT) at birth (postnatal day 0; P-0) resulted in an abnormal terminal distribution of the uncrossed retinotectal projection. The present study provided further evidence to support the role of increased 5-HT levels within the SC in this phenomenon. Slow-release polymer (ELVAX) chips impregnated with serotonin (5-HT) were placed over the SC on either P-1 or P-3, and retinotectal projections were assessed via anterograde transport of horseradish peroxidase when animals reached P > 18. Analysis of ELVAX chips indicated that they released 5-HT in amounts of > or = 1 pmole/hour for at least 12 days. Assessment of the SC of treated hamsters indicated significantly elevated 5-HT concentrations as late as P-12, but not on P-16. Implantation of 5-HT chips, but not control chips, resulted in abnormalities in the uncrossed retinotectal projection similar to those observed in the 5,7-DHT-treated animals. The patches that normally develop in the rostral part of the stratum opticum were not present, and uncrossed axons were distributed densely in this layer and in the lower portion of the stratum griseum superficiale throughout the rostrocaudal and mediolateral extents of the SC. Quantitative analysis of these changes indicated significant differences between the organization of the uncrossed retinotectal projections of 5-HT-treated animals vs. either blank-implant treated or completely untreated animals but not between 5-HT-treated hamsters and animals that received neonatal 5,7-DHT injections. All of these results support the conclusion that increased SC concentrations of 5-HT altered retinotectal development.

Animals↗