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Isolation of the Drosophila segmentation gene runt and analysis of its expression during embryogenesis.

runt is one of the genes required for establishment of the segmented body pattern of the Drosophila embryo. We have isolated DNA sequences containing this gene using P-element transposon tagging. Southern blot analyses of six different DNA rearrangements that are associated with runt mutations revealed a minimal region of 8.5-kb of DNA that was important for function. In germ line transformation experiments, a 14.5-kb segment of DNA that spanned this minimal region provided significant, although not full, levels of runt activity. The runt gene encoded a 2.6-kb poly(A)+ RNA that underwent a series of dynamic changes in its spatial and temporal patterns of accumulation during embryogenesis. The runt RNA was most abundant at the blastoderm stage when it showed the seven stripes of expression characteristic of other Drosophila pair-rule genes.

Animals

The Drosophila segmentation gene runt encodes a novel nuclear regulatory protein that is also expressed in the developing nervous system.

Generation of the anterior-posterior body pattern in the Drosophila embryo requires the activity of the segmentation genes. The segmentation gene runt has been classified as one of the primary pair-rule genes because of the pivotal role it plays in regulating the expression of other pair-rule genes. Here, we present the structure of this gene and describe the pattern of runt protein expression during embryogenesis. The deduced protein sequence shows no obvious overall homology with any sequences in the data base. The absence of an identifiable transcription factor motif (e.g., homeo box, zinc finger, leucine zipper, or helix-loop-helix) makes runt different from the other early-acting segmentation proteins. A runt-specific polyclonal antibody was generated and used to demonstrate that the subcellular location of the protein is in the nucleus. Double-staining immunolocalization experiments were used to determine the overlap of the runt protein pattern with the patterns of the pair-rule genes hairy (h), even-skipped (eve), and fushi tarazu (ftz). We found that the patterns of runt and hairy are complementary. Their phasing is shifted anteriorly by two cell diameters with respect to the complementary eve and ftz patterns. Experiments with the runt antibody also indicated that the protein is present throughout embryogenesis and is expressed extensively in the developing central and peripheral nervous system.

Amino Acid Sequence

Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system.

The gap genes of Drosophila are the first zygotic genes to respond to the maternal positional signals and establish the body pattern along the anterior-posterior axis. The gap gene knirps, required for patterning in the posterior region of the embryo, can be activated throughout the wild-type embryo and is normally repressed from the anterior and posterior sides. These results provide direct molecular evidence that the posterior morphogen system interacts in a fundamentally different manner than do hunchback and bicoid, which are responsible for anterior pattern formation.

Animals

Anterior determinants in embryos of Chironomus samoensis: characterization by rescue bioassay.

Embryos of Chironomus samoensis are programmed, by anterior u.v. irradiation, to form the abnormal body pattern 'double abdomen'. Most double abdomen embryos show a mirror-image duplication of abdominal segments in the absence of cephalic or thoracic segments. Such embryos can be 'rescued', i.e. restored to normal development, by microinjection of cytoplasm or RNA from unirradiated donor embryos. Most of the rescued embryos look completely normal and many of them hatch spontaneously. The rescuing activity decreases from the anterior to the posterior pole in the donor cytoplasm and must be delivered near the anterior pole of the recipient for maximum efficiency. Rescuing activity is present in total RNA extracted from whole, unirradiated embryos. Upon fractionation, the activity is associated with poly(A)+ RNA, with LiCl precipitate depleted of RNA smaller than 250 nucleotides (nt) and with a sucrose gradient fraction depleted of RNA larger than 500 nt. Corresponding fractions of RNA from Xenopus oocytes have no rescuing activity. The activity of Chironomus RNA is sensitive to u.v. irradiation with low fluence affecting less than 2% of the pyrimidine bases. Rescuing activity is present in cytoplasm until the blastoderm stage but disappears earlier from poly(A)+ RNA. Rescuing activity is also present, and localized, in cytoplasm of embryos from two related dipterans, Smittia sp. and Drosophila melanogaster, although the extent of rescue observed in Chironomus decreases with the phylogenetic distance between donor and recipient. The results of these and previous experiments indicate that dipteran embryos contain localized RNP particles acting as anterior determinants. In Chironomus, the activity of these particles seems to depend on the integrity of polyadenylated RNA of about 250 to 500 nt length.

Abdomen

Potentiation by the lithium ion of morphogenetic responses to a Xenopus inducing factor.

We have cultured explants of Xenopus blastular animal cap tissue from embryos that had received an earlier treatment with LiCl and from their untreated siblings, in various concentrations of XTC-cell-derived mesoderm-inducing factor (XTC-MIF, Smith, 1987; Smith et al. 1988). The pretreatment with lithium that we used transforms later morphogenesis in the whole embryo to give radialized body forms with anterior/dorsal levels of structure grossly over-represented. In addition, animal caps from 'Li+' embryos were allowed to develop without exposure to in vitro MIF (Li+ controls) and compared with normal uninduced control explants, and explants were made from normal early blastulae but given various initial treatments with LiCl in culture. The results confirm that the lithium ion itself will not induce mesoderm in competent, animal cap tissue of Xenopus. It does, however, enhance the responsiveness of this tissue to XTC-MIF, in a way that parallels its recently reported effect in the case of another mesoderm inducer of different character, bFGF (Slack et al. 1988). The effects observed are sufficient to imply that the altered body pattern that follows lithium treatment, in whole embryos, could be caused by modulation of the responses to an unaltered pattern of in situ inductive stimuli. We also observe evidence that appreciable inductive signals reach animal pole tissue beyond the limits of mesoderm formation in normal development. Relatively low concentrations of MIF prevent the development of an epidermis-specific marker in dissociated blastular animal cap cells (Symes et al. 1988). When such experiments are repeated in relation to the lithium pretreatment of embryos, such treatment is seen to have sensitized the cell population, so that the MIF concentration range that assures complete suppression of the marker is reduced. The results are discussed in relation to induction considered as pattern formation.

Animals

The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.

Mesoderm in Xenopus and other amphibian embryos is induced by signals from the vegetal hemisphere acting on equatorial or animal hemisphere cells. These signals are diffusible and two classes of candidate signal molecule have been identified: the fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) types. In this paper, we compare the effects of cloned Xenopus basic FGF (XbFGF) and electophoretically homogeneous XTC-MIF (a TGF-beta-like factor obtained from a Xenopus cell line) on animal pole explants. We find that they have a similar minimum active concentration (0.1-0.2 ng ml-1) but that, nonetheless, XTC-MIF is at least 40 times more active in inducing muscle. In general, we find that the two factors cause inductions of significantly different characters in terms of tissue type, morphology, gene expression and timing. At low concentrations (0.1-1.0 ng ml-1) both factors induce the differentiation of 'mesenchyme' and 'mesothelium' as well as blood-like cells. These latter cells do not, however, react with an antibody to Xenopus globin. This raised the possibility that the identification of red blood cells in other studies on mesoderm induction might have been mistaken, but combinations of animal pole regions with ventral vegetal pole regions confirmed that genuine erythrocytes are formed. The identity of the blood-like cells formed in response to the inducing factors remains unknown. At higher concentrations XTC-MIF induces neural tissue, notochord, pronephros and substantial and often segmented muscle. By contrast, XbFGF only induces significant amounts of muscle above 24 ng ml-1 and even then this is much less than that induced by XTC-MIF. For both factors an exposure of less than 30 min is effective. Competence of animal pole cells to respond to XbFGF is completely lost by the beginning of gastrulation (stage 10) while competence to XTC-MIF is detectable until somewhat later (stage 11). Since animal pole tissue is known to be able to respond to the natural inducer at least until stage 10, and perhaps until stage 10.5, this suggests that bFGF cannot be the sole inducer of mesoderm in vivo. Taken together, these results are consistent with XTC-MIF being a dorsoanterior inducer and XbFGF a ventroposterior inducer, suggesting that body pattern is established by the interaction of two types of inducing signal. This model is discussed in view of the qualitative and quantitative differences between the factors.

Animals

Control of segmental asymmetry in Drosophila embryos.

During Drosophila development, an important aspect of body patterning is the division of the embryo into repeating morphological units referred to as parasegments. The parasegmental domains are first defined at the blastoderm stage by alternating stripes of transcripts encoded by the pair-rule genes fushi tarazu (ftz) and even-skipped (eve) and later by stripes encoded by the segment polarity genes engrailed (en) and wingless. Here, we show that the runt gene (run) is required to generate asymmetries within these parasegmental domains. Using a heat-shock-inducible run transgene, we found that ectopic run expression leads to rapid repression of eve stripes and a somewhat delayed expansion of ftz stripes. Unexpectedly, we also found that ectopic run was a rapid and potent repressor of odd-numbered en stripes. Two remarkably different segmental phenotypes were generated as a consequence of these effects. In solving the mechanisms underlying these phenotypes, we discovered that the positioning of en stripes is largely determined by the actions of negative regulators. Our data indicate that run is required to limit the domains of en expression in the odd-numbered parasegments, while the odd-skipped gene is required to limit the domains of en expression in the even-numbered parasegments. Activation of en at the anterior margins of both sets of parasegments requires the repression of run and odd by the product of the eve gene. The spatial restriction of gene expression via negative and double negative pathways such as these is likely to be a common theme during development.

Animals

Mitotic delay dependent survival identifies components of cell cycle control in the Drosophila blastoderm.

The Drosophila body pattern is laid down by maternal and zygotic factors which act during the early phase of embryonic development. During this period, nascent zygotic transcripts longer than about 6 kilobases are aborted between the rapid mitotic cycles. Resurrector1 (Res1) and Godzilla1 (God1), two newly identified dominant zygotic suppressor mutations, and a heterozygous maternal deficiency of the cyclin B locus, complement the partial loss of function of the segmentation gene knirps (kni) by extending the length of mitotic cycles at blastoderm. The mitotic delay caused by Res1 and God1 zygotically and by the deficiency of the cyclin B locus maternally allows the expression of a much longer transcript of a kni cognate gene normally aborted between the short mitotic cycles and consequently allows survival of kni mutant progeny. In addition to the practical benefits of identifying mutations in Drosophila cell cycle regulatory genes as suppressors of kni, our results have evolutionary implications regarding the flexibility of the genome to meet sudden selective pressures by recruiting cognate genes to function.

Animals

Transcriptional control by Drosophila gap genes.

The segmented body pattern along the longitudinal axis of the Drosophila embryo is established by a cascade of specific transcription factor activities. This cascade is initiated by maternal gene products that are localized at the polar regions of the egg. The initial long-range positional information of the maternal factors, which are transcription factors (or are factors which activate or localize transcription factors), is transferred through the activity of the zygotic segmentation genes. The gap genes act at the top of this regulatory hierarchy. Expression of the gap genes occurs in discrete domains along the longitudinal axis of the preblastoderm and defines specific, overlapping sets of segment primordia. Their protein products, which are DNA-binding transcription factors mostly of the zinc finger type, form broad and overlapping concentration gradients which are controlled by maternal factors and by mutual interactions between the gap genes themselves. Once established, these overlapping gap protein gradients provide spatial cues which generate the repeated pattern of the subordinate pair-rule gene expression, thereby blue-printing the pattern of segmental units in the blastoderm embryo. Our results show different strategies by which maternal gene products, in combination with various gap gene proteins, provide position-dependent sets of transcriptional activator/repressor systems which regulate the spatial pattern of specific gap gene expression. Region-specific combinations of different transcription factors that derive from localized gap gene expression eventually generate the periodic pattern of pair-rule gene expression by the direct interaction with individual cis-acting "stripe elements" of particular pair-rule gene promoters. Thus, the developmental fate of blastoderm cells is programmed according to their position within the anterior-posterior axis of the embryo: maternal transcription factors regulate the region-specific expression of first zygotic transcription factors which, by their specific and unique combinations, control subordinate zygotic transcription factors, thereby subdividing the embryo into increasingly smaller units later seen in the larva.

Animals

Behavioral assessment scale of oral functions in feeding.

When implementing therapeutic feeding programs for the multiply-handicapped developmentally disabled, it is imperative to establish a specific baseline of observable oral movement upon which management and change can be measured. The assessment reported provides an objective and graded method of documenting the major aspects of oral function in relation to feeding difficulties. It is designed to be used in conjunction with an assessment of overall muscle tone and body patterns and an evaluation of specific oral structures and deviations that might interfere with eating.

Adolescent

[Association of lichen planus and discoid lupus erythematosus. A clinical and histopathological study of 2 cases].

Two patients showing features of both lichen planus and lupus erythematosus are described: reticular whitish patches in the oral mucosa coexisting with chronic, partly atrophic LED-like skin lesions located on the face were present in both of them. The histological, histochemical and immunopathological findings allowed to diagnose a "LP-LE coexistence" more than a mixed LP-LE disease. The clinical, histological and immunological relationships between LP and LE are discussed and it is suggested that the pathogenesis of the coexistence of the two diseases could be related to a common pathophysiological pathway. It might be that LP and LE are due to a single aetiological agent (e.g. a virus) interacting with different genetic backgrounds to cause LE in some, LP in others and an intermediate disease in a small group of patients. The histopathological and immunopathological features that distinguish LP from LE are the concentration of lymphocytes in areas of keratinocyte damage, the different colloid bodies patterns and the direct IF findings. The Authors conclude that further studies should be performed on "LP-LE coexistence".

Adult

[Urinary incontinence and prolapse. Medical treatment and functional treatment].

Urinary continence implies that the variations of the vesical pressure does not exceed the capacities of the cervico-urethral closure system. The aim of the various methods of treatment is to have a beneficial action on those two parameters: drug therapy will mainly reduce the intra-vesical pressure (parasympatholytics...) and also improve the urethral tone (alpha-adrenergics...), or have a mixed effect on both systems (tricyclic antidepressants, oestrogens...). The side effects are often numerous due to the impact on the vegetative or neuromuscular system. The re-education is complemented by: local and general kinesitherapy, sensorial retrocontrol, associated or not to electrotherapy. Motivation and active participation of the patient are essential. The indications covers all the various pathologies (perineal insufficiency, defects in the body pattern, prolapse, sphincteral insufficiency, transmission problems, vesical instability, urethral instability) and concerns patients of all age groups.

Biofeedback, Psychology

Subtypes in major depression without melancholia.

Using the Diagnostic and Statistical Manual of Mental Disorders (DSM III, 1980) criteria to diagnose major depression without melancholia, 70 adult patients were selected for further detailed clinical and neuro-endocrinological evaluation. Two subtypes emerged; changes in sleeping patterns, body mass and thyrotrophin response to thyrotrophin-releasing hormone constituted the distinguishing features between the two categories (P = 0.012).

Adult

General pharmacology of brotizolam in animals.

Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin) is a thienotriazolo-diazepine with profound sedative and hypnogenic properties. The side effects of the drug on general behavior, motocoordination, feeding pattern, body temperature, uropoietic and gastrointestinal functions, cardiovascular system, and respiration, as well as interactions with some biogenic amines are reported and discussed. The findings correlate with those known for other diazepines. Accordingly, effects on motocoordination were prominent, but were limited to an ataxia, whereas even extremely high doses scarcely eliminated the postural reflexes. Sleeping animals could invariably be woken and were capable of locomotion; thus, no comatose condition developed. The cardiovascular functions were not appreciably altered by brotizolam in anesthetized cats, while in conscious dogs minor fluctuations of blood pressure and heart rate occurred. Respiration was clearly inhibited when brotizolam was given intravenously. The cardiovascular effects of acetylcholine, norepinephrine, epinephrine, isoprenaline, and histamine were only slightly modulated. The orexigenic and hypothermic effects equalled those of other diazepines. The functions of kidney, stomach, and intestines were not affected. The entirety of the observations procured in ten different species suggest that brotizolam is well tolerated when given orally.

Animals

[Quantity of DNA, sex chromatin bodies and nucleoli in the nuclei of the muscle cells of normal and hypertrophied human atria].

Nuclei of myocytes of normal and hypertrophied human heart atrium were studied on squash preparations. Judging by the sex chromatin body pattern, it is the polyploidization that is responsible for the increased DNA contents in these nuclei. The cytophotometric DNA measurements demonstrated the up to 93% occurrence of polyploid nuclei even in myocytes of normal atrium. Myocytes of hypertrophied atrium contained nuclei of higher ploidy degrees. The total area of nucleoli per nucleus was shown to be proportional to a degree of ploidy.

Adult

[Hemophilia: evaluation of the nutritional status and growth in childhood].

Haemophilia is a bleeding disorder characterized by decreased activity of the circulating antihemophilic factor, with different degrees of severity. The prognosis of the disease for an useful normal life is good, providing an adeguate follow-up. We think that the auxological determinants of growth and nutritional status must enter as points of a multicentre follow-up sheet of haemophilia in the pediatric age. We have tried such an approach in 13 patients; preliminary results have shown that all patients are growing well with some degrees of discrete malnutrition (arm circumference less than -1.6 SD). From costitutional point of view, haemophilic boys show a discrete "lean" body pattern (W/H2 less than or equal to O SD(with their trunk longer than legs. Data from other studies are wellcome for confirming our first impressions.

Anthropometry

Cancer of the prostate: treatment and nursing implications.

PURPOSE/OBJECTIVES: To review the clinical manifestations, current treatment, and nursing management of prostate cancer. DATA SOURCES: Published articles, book chapters, American Cancer Society booklets. DATA SYNTHESIS: Prostate cancer is a slow-growing malignancy and usually is asymptomatic in its early stages. It causes acute urinary obstruction at more advanced stages, and patients may present with metastatic disease. Diagnosis is made by biopsy, and treatment options include periodic observation, surgery, radiotherapy hormonal manipulation, and chemotherapy with standard or investigational drugs or combination therapy. The major complications associated with surgery and radiation therapy are transient or permanent incontinence and impotence. CONCLUSIONS: Because no definitive method for identifying clinically important lesions exists, much controversy surrounds prostate cancer treatment. Issues significant to the diagnosis and treatment of all stages of prostate cancer are identified, and nursing care concerns focusing on treatment and disease-related problems are presented. IMPLICATIONS FOR NURSING PRACTICE: Nursing care focuses on providing patients with accurate information to make informed decisions regarding treatment for early stage disease, on promoting comfort, and on preventing and managing treatment and disease-related complications. Nursing diagnoses include knowledge deficit; altered sexual patterns, body image disturbance, altered urinary elimination, diarrhea, impaired skin integrity, and pain, fatigue, bleeding, and infection, all of which are related to surgery, pathologic fractures, spinal cord compression, and edema of the scrotum/lower extremities.

Humans

Stature and body weight growth patterns from longitudinal data of Japanese children born during World War II.

Stature and body weight data of 100 boys and 100 girls from 7 to 17 years of age in Shimodate City who were born during World War II were longitudinally analyzed. The children were significantly smaller and lighter throughout their growth period than those born 11 years after the end of the war. The correlation coefficient between statures at each age and at age 17 showed a gradual increase with increasing age, while that between statures at each age and at age 7 decreased with age. However, a drop in the correlation coefficient was found during puberty, at age 11 for girls and at age 13 for boys. Comparing the normalized distance from mean values of stature and body weight at age 7, at puberty, and at age 17, only 51% of the children continued to be in the same relative position for both height and weight, 6% of boys and 4% of girls showing a decreasing pattern for both and 4% of boys and 7% of girls showing an increasing pattern for both. Thus, about 60% of the children of either sex presented parallel stature and body weight growth patterns for ages from 7 to 17.

Adolescent