SEARCH · PubMed Health

Results for “Developmental programming”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,621 records · Page 90Linked to original sources

PubMed1988

Correlation of immunophenotype with rearrangement of T cell antigen receptor beta and gamma genes in acute lymphoblastic leukemia of adults.

The structure of immunoglobulin heavy chain (IgH) and T cell antigen receptor (TCR) beta and gamma chain genes was studied in 38 cases of adult and two cases of childhood acute lymphoblastic leukemia (ALL). Seven cases of T-ALL all showed clonally rearranged TCR beta and gamma genes; only one of these also contained rearranged IgH genes. All precursor B cell ALLs and one case of unusual B cell ALL/lymphoma had clonally rearranged IgH genes, but a high proportion (22 of 32, 69%) of precursor B cell ALLs also had rearrangement of TCR beta and/or gamma genes. TCR beta gene rearrangement was less common in more mature precursor B cell ALL, expressing cytoplasmic IgM (pre-B-ALL) (0 of 5) than in other precursor B cell ALL cases (15 of 27). In the precursor B cell ALLs overall, 10 (32%) had rearrangement of both beta and gamma genes, while 7 (22%) had rearrangement of TCR gamma genes only. A further 5 (16%), all expressing one or more unusual immunophenotype markers, had TCR beta gene rearrangement without detectable gamma gene rearrangement. These observations, together with certain characteristics of constant-joining region usage of both TCR genes (a preference for rearrangement into the C beta 2 and C gamma 1 genes), distinguishes these "inappropriate" rearrangements from those found in T-ALL and suggests that they have arisen through a differentiation arrest which is not part of a normal T cell developmental program.

Acute Disease↗

PubMed1987

Numerical matching during cerebellar development: quantitative analysis of granule cell death in staggerer mouse chimeras.

Cell death is a common yet puzzling feature of the development of many populations of neurons in the CNS. In the invertebrate phyla, such death is often preprogrammed; by contrast, in vertebrates, the best studied examples of histogenetic cell death are influenced by interactions among the neurons and their target. One attempt to explain this seemingly wasteful scheme of development has led to the hypothesis that this target-related cell death allows 2 populations of cells, which develop in isolation, to come into numerical and functional balance and hence to provide an epigenetic "buffer" mechanism to accommodate developmental variations. In the current study we have examined the extent to which the cell death observed in the cerebellar granule cell population serves to numerically match these neurons with their primary postsynaptic target, the Purkinje cell. Staggerer chimeras were made by aggregating 8-cell staggerer embryos with embryos of wild-type genotype. The cerebella of the resulting animals developed with widely varying numbers of normal (wild-type) Purkinje cell targets. Although staggerer Purkinje cells were present in the chimeric brains, these cells are intrinsically deficient in their normal developmental program (in the mutant, because of this deficiency, 100% of the granule cells die). Both granule cells and Purkinje cells were counted in chimeras and several wild-type mice. The results reveal that the number of granule cells present in these brains has a linear relationship with the number of Purkinje cells, and that the line connecting the points intersects the Y-axis close to the origin. These observations suggest that numerical matching is an important function of target-related cell death in the granule cell population.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Palatal development and the arachidonic acid cascade.

The production of cleft palate by glucocorticoids and phenytoin is a complicated interference of a complex developmental program involving many genetic and biochemical processes. The H-2 histocompatibility region includes genes which affect susceptibility to glucocorticoid- and phenytoin-induced cleft palate; glucocorticoid receptor level in a variety of tissues including maternal and embryonic palates, adult thymuses and lungs; and the degree of inhibition of prostaglandin and thromboxane production by glucocorticoids and phenytoin in thymocytes. A gene linked to a minor histocompatibility locus (H-3) on the second chromosome also influences susceptibility to glucocorticoid and phenytoin-induced cleft palate. Phenytoin is an alternate ligand for the glucocorticoid receptor affecting prostaglandin and/or thromboxane production. The capacity of glucocorticoids to induce cleft palate is correlated with their anti-inflammatory potency. At least some of the anti-inflammatory effects of glucocorticoids can be explained by the inhibition of prostaglandin and/or thromboxane release, which in turn could be caused by inhibition of arachidonic acid release from phospholipids. Similar mechanisms may be involved in cleft palate induction, as exogenous arachidonic acid injected into pregnant rats and mice at the same time as glucocorticoids reduces the teratogenic potency of the steroids and indomethacin, and inhibitor of cyclooxygenase, blocks the corrective action of arachidonic acid. Glucocorticoids and phenytoin cause a delay in shelf elevation, and this delay is promoted by fetal membranes and the tongue. However, the cells of the medial edge epithelium are programmed to die whether contact is made with the apposing shelf or not. Glucocorticoids and phenytoin interfere with this programmed cell death, and this interference by both drugs seems to be a glucocorticoid receptor mediated event, to require protein synthesis and to be related to arachidonic acid release.

Animals↗

PubMed1980

Cell-cell recognition.

The earlier step of morphogenesis is the segregation of cell lines which are homogeneous cell populations each endowed with its own specific developmental program. In order for the program to unfold in each line cells must be endowed with specific surface properties whereby the cells belonging to the same line can recognize each other as such in addition to recognizing those belonging to other cell lines as different. Experiments supporting this view are described. The hypothesis is presented that the cell-cell recognition system is phylogenetically linked with the invention of sexuality.

Animals↗

PubMed1980

Regulation of glyoxysomal enzymes during germination of cucumber. Temporal changes in translatable mRNAs for isocitrate lyase and malate synthase.

The relative levels of translatable messenger RNA for isocitrate lyase and malate synthase were determined in the dry seed and for the first seven days of development of cucumber cotyledons. After extraction and quantification of total and poly(A)-rich RNA each day, the RNA fractions were translated in an optimized wheat germ system and the specific polypeptides were immunoprecipitated quantitatively. The radiolabeled isocitrate lyase and malate synthase polypeptides were then fractionated on dodecylsulphate/polyacrylamide gels, visualized by exposure to X-ray film and quantified densitometrically. The relative levels of translatable messenger RNA for these enzymes rise and fall with a developmental program similar to the enzyme activities, but preceding the latter by about one day. This implies that the rise in enzyme activity is dependent upon a prior postgerminative increase in translatable messenger RNA for the enzymes. These studies also suggest that messenger RNA levels may be regulated, at least in part, by light.

Glyoxylates↗

PubMed1984

Dieting. Ideology versus physiology.

The author examines the phenomenon of dieting among the general public and among patients with weight problems. Setpoint and fiscal models are discussed and developmental programs, chemical regulators, endogenous and structural changes in the central nervous system, and sensory stimuli are detailed.

Adipose Tissue↗

PubMed1995

The olfactory and visual systems are closely related in Drosophila.

The olfactory and visual systems of Drosophila have similar developmental origins: both derived from the eye-antennal imaginal disc. Moreover, there are commonalities in the cellular, molecular, and genetic underpinnings of their development. For example, the developmental program of both systems entails cell death, which depends upon the irregular chiasm C-roughest gene, and both systems require the lozenge gene for normal pattern formation. The rdgB (retinal degeneration B) gene is required not only for the maintenance and physiology of the visual system, but also for olfactory physiology. This gene has been shown by others to encode a phosphatidylinositol transfer protein; it is expressed both in visual and olfactory organs. The norpA gene, which encodes a phospholipase C, is also required both for phototransduction and for odorant response in one olfactory organ. Thus some genes are required in both systems; in addition, at least one olfactory gene that is apparently not expressed in the visual system may have a visual system counterpart. These and other similarities are considered in terms of the evolutionary relationship between the two systems. We conclude that analysis of the visual system is likely to provide insight into the development and function of the olfactory system, and vice versa.

Animals↗

PubMed1995

[Perinatal pharmacotherapy and the risk of functional teratogenic defects].

Perinatal period, which is characterized by intensive histogenesis and cytodifferentiation of the already shaped organs, is a highly vulnerable phase for fetal/neonatal brain and immune system-organs with high similarity in receptor equipment. Even fine deviations in the programmed developmental processes induced by drugs initiate disorders in the formation of neural network, cytoarchitectonics and receptor-transmitter communication systems. This pathology is not evident at birth, but forms the basis for various functional defects of neuro-psycho-immunocompetence which become apparent gradually during further maturation or even in adulthood. Clinical recognition of such functional teratogenic action of drugs is hampered by the long time interval (upto decades) between the drug administration and its consequences, making the identification of causal relations very difficult. Consequently, experimental research is necessary under the precondition of adequate animal models with sufficient validity for the extrapolation on human level. The authors suggest the principles of such approach using drug application in neonatal rats with lifelong follow-up of behaviour, immune reactivity and brain biochemical analysis. The evaluation of functional teratogenic risk in three drugs used in the treatment of risk pregnancies and risk neonates (dexamethazone, fenoterol, diazepam) is presented.

Abnormalities, Drug-Induced↗

PubMed1995

Mitogen activation of a nuclear alkaline phosphatase in normal activated lymphocytes.

B cell differentiation is punctuated by V(D)J joining in the heavy chain of the pro-B cell, VJ joining in the light chain of the pre-B cell, switch recombination, and somatic hypermutation in the mature B cell. The regulatory signals controlling these events and the developmental program leading to them is poorly understood. We have identified a new phosphatase activity that is expressed in lymphocytes and for which high expression is restricted to mature B cells. This new phosphatase is transiently expressed in nuclear extracts of mitogen-activated splenic B cells. The phosphatase is a monoesterase that is active on both dNMPs and pNPP. The phosphatase has been partially purified by column chromatography and is inhibited by orthovanadate, molybdate, tetramisole, and EDTA and requires Mn2+ for activation. Monoesterase activity requires a pH above the neutral range. The activity profile in the presence of the inhibitors and the requirement for basic pH suggest that this enzyme is an alkaline phosphatase.

Alkaline Phosphatase↗

PubMed1994

The control of spatial organization during cellular differentiation.

Caulobacter crescentus is a dimorphic bacterium that yields two distinct cell types with every cell division, a motile swarmer cell and a sessile stalked cell. Caulobacter, therefore, possesses a simple developmental program and is used as an model system to determine basic mechanisms of cellular morphogenesis. The generation of the asymmetric predivisional cell requires the temporal expression of many genes as well as the precise intracellular positioning of these gene products. Analysis of the biogenesis and positioning of cell type-specific genes and proteins has been instrumental in understanding the underlying principles as to how asymmetry in the predivisional cell is generated. This manuscript explores our current understanding of the mechanisms by which Caulobacter differentiation is achieved.

Bacterial Proteins↗

PubMed1993

Developmental variation in the structure of the retina.

Events traditionally called "developmental errors" are known to occur in both vertebrate and invertebrate nervous systems. This study was concerned with the frequency and mode of generation of such events in the mammalian retina. We studied three anomalous structures observed in the rabbit's retina after staining of the cell populations that accumulate indoleamines: type 3 cells, stray processes in the optic fiber layer, and displaced cells. They were counted in rabbit retinas prepared as whole-mounts, and in most cases topological maps were made. For comparison, the conventional indoleamine-accumulating amacrine cells and the tyrosine hydroxylase (TH)-positive cells, which are members of the mammalian retina's recognized complement of amacrine cells, were also counted. A further comparison was made with the number and distribution of TH-positive amacrine cells in highly inbred mice. The ordinary amacrine cells did not vary much in number from animal to animal. Especially in inbred mice, the reproducibility was striking: the extreme variation in number of TH amacrine cells between any two of the 14 retinas studied was 22%, and the mean difference between two eyes of individual mice was 2.5 +/- 1.7%. The three anomalous structures were rare and variable. Their numbers varied more than fourfold from animal to animal. However, their numbers in two eyes from the same animal varied by an overall average of only 14 +/- 10%. The anomalous structures were present in all rabbits, and their morphology was the same in all cases: they are under precise control by the developmental program. The anomalous cells share many phenotypic features with the regular amacrine cells of the indoleamine-accumulating class.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗

PubMedDate not supplied

Lipopolysaccharides (LPS), up-regulate the IL-1-mRNA and down-regulate the glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS)-mRNAs in astroglial primary cultures.

The effect of lipopolysaccharides (LPS), a component of gram-negative bacteria, has been studied in both exponentially growing and confluent morphologically differentiated astroglial cells in primary cultures. The expression of glial fibrillary acidic protein (GFAP) and Glutamine Synthetase (GS) were investigated in parallel with proliferation and expression of IL-1 beta-mRNA. During the exponential growth, proliferation was severely inhibited by LPS. The effect was time- and dose-dependent. On confluent differentiated cells LPS induced an inhibition of cell proliferation which was associated with a down-regulation of GFAP-mRNA, GS-mRNA and GS expressions and with a transitory increase in IL-1 beta mRNA expression. The observed effects might interact with the astroglial developmental program and with the astroglial function.

Animals↗

PubMed1993

Regulation of kidney organogenesis: homeobox genes, growth factors, and Wilms tumor.

Factors regulating the temporal and spatial expression of kidney developmental programs are beginning to be identified. Evidence accumulated in the past few years indicates that the Hox and Pax genes, in particular, are important for early kidney development. A number of soluble growth factors were also shown to be essential for nephrogenesis to proceed in vitro. Errors in kidney development include Wilms tumor, a common childhood malignancy, which in many cases seems to be caused by faulty transcriptional regulation.

Genes, Homeobox↗

PubMed1994

Expression of gelatinase A, a mediator of extracellular matrix remodeling, by tracheal gland serous cells in culture and in vivo.

Tracheal gland morphogenesis and gland hypertrophy in disease involve the penetration of epithelial cells into the submucosa, a process that requires digestion of the basal lamina and the surrounding extracellular matrix. We observed that bovine tracheal gland cells invaded collagen substrates and were inhibited from doing so in the presence of a metalloproteinase inhibitor GM6001. The gland cells, but not bovine tracheal surface epithelial cells, secreted a 72-kDa metalloproteinase. The purified enzyme could be activated with 4-aminophenylmercuric acetate and converted to an active 65-kDa form that was far more effective in degrading denatured collagen (gelatin) than nondenatured type I and IV collagens and was ineffective in degrading intact interstitial collagen fibers. At 25 degrees C, the initial rate of degradation of acid-solubilized type I collagen was approximately 50 mg of type I collagen cleaved per min per mg of enzyme, whereas acid-solubilized type IV collagen was degraded at approximately 250 mg cleaved per min per mg of enzyme. In contrast, at the same temperature, heat-denatured type I collagen was degraded 1000-fold more rapidly, while heat-denatured type IV collagen was cleaved 50-fold more rapidly. The activity of the enzyme was maximal at pH 7-8 and was completely abolished by the metalloproteinase inhibitors EDTA and 1,10-phenanthroline. In immunoblots, the enzyme was recognized by an antibody directed against human gelatinase A, the 72-kDa gelatinase. The purified enzyme disrupted the distribution pattern of type IV collagen in the gland basal lamina, as well as of interstitial collagen in the underlying stromal tissue, as shown in tissue sections by immunocytochemistry. Using an antibody directed against the purified enzyme, we also showed by immunocytochemistry that the gelatinase was present in tracheal tissue and was specifically located at the periphery of some tracheal gland acini. Northern blots showed higher concentrations of gelatinase A mRNA in glands than in epithelium microdissected from adult cow tracheas. These data indicate that gelatinase A is a specialized product of the tracheal gland epithelial cell, a cell type normally invasive as part of its developmental program; the enzyme may play an important role in normal gland development and disease-associated hypertrophy.

Animals↗

PubMed1994

Hox genes in normal and neoplastic mouse mammary gland.

Homeobox-containing genes regulate embryonic developmental programs and are expressed in certain adult tissues and cancers. There has been no report of expression in the breast. We amplified homeobox complementary DNA from mouse mammary gland and found expression of members from each of the four major Hox gene clusters. The regulation of expression of two Hox genes was examined in greater depth. Hoxc-6 transcripts were present in the glands of pubescent and mature mice and decreased during pregnancy. Levels were increased substantially following ovariectomy, indicating possible negative regulation by steroid hormones. Hox expression was studied in mammary adenocarcinomas and in transplant lines of the benign, precancerous tissues from which the cancers arose. Hoxc-6 was expressed at low levels in the precancerous tissue but was not expressed in cancers. In contrast, Hoxa-1 was expressed only in cancers, not in normal gland or in precancerous mammary tissues, suggesting that Hox genes may play a role in a late stage in the stepwise development of mammary malignancies.

Amino Acid Sequence↗

PubMed1994

Random chimeragenesis of G-protein-coupled receptors. Mapping the affinity of the cAMP chemoattractant receptors in Dictyostelium.

G-protein-coupled receptors mediate a wide variety of responses to extracellular stimuli in eucaryotic cells. Binding of the ligand to these receptors is thought to involve contacts within a pocket from the sequences of these genes. A family of four surface cAMP receptors that mediate responses to secreted cAMP coordinates the developmental program of Dictyostelium. A large difference in affinity for cAMP exists between cAR1 (25 and 230 nM) and cAR2 (> 5 microns). To understand the basis for this affinity difference, we generated an extensive series of cAR1/cAR2 and cAR2/cAR1 chimeras using a technique designated "random chimeragenesis." When a linearized plasmid was transformed into Escherichia coli, tandemly positioned cAR1 and cAR2 genes crossed over at homologous regions. The cAMP binding properties and EC50 values for agonist-induced phosphorylation of each of the chimeras were characterized in order to map the domains that determine the affinity. These studies implicated a domain in the second extracellular loop in which only 5 residues differ between the two receptors as the major determinant of affinity. A secondary domain including residues 110-147 (11 residue differences) was identified as a minor determinant of affinity.

Animals↗

PubMed1994

A germ line-specific sequence element in an intron in Tetrahymena thermophila.

In the ciliated protozoa, the germ line micronucleus carries DNA sequences that are eliminated during the developmental program that produces the somatic macronucleus. We have identified such a micronuclear element in an intron of a gene in the holotrichous ciliate, Tetrahymena thermophila. The macronuclear version of this gene, numbered from the transcription initiation site to the polyadenylation site, is 1569 nucleotides long and contains two introns: intron 1 from nucleotides 206 to 382 and intron 2 from nucleotides 665 to 898. The gene is transcribed into a stable polyadenylated mRNA which is predicted to encode a polypeptide with a highly repetitive structure and an unknown function. The micronuclear version of the gene contains a 2.9-kb sequence element, mse2.9, in intron 2. This element was characterized by sequencing two micronuclear genomic clones that contain 909 and 764 base pairs of micronucleus-specific sequence from its left and right ends, respectively. This sequence has an (A+T) content of 81% and is present as a single copy. The termini of mse2.9 are located within a 4-nucleotide direct repeat, TTAT, one copy of which is retained in the macronuclear gene, between positions 755 and 759. Other features near the termini of mse2.9 include a GC-rich sequence motif, CCAACCCGTTG, 31 nucleotides outside the left terminus and a 20-nucleotide palindrome 6 nucleotides outside the right terminus.

Amino Acid Sequence↗

PubMed1994

Mouse fetal liver cells lack functional amphotropic retroviral receptors.

We have been transducing mouse hematopoietic cells with the human MDR1 (MDR) gene in retroviral vectors to determine the optimal conditions for retroviral gene transfer as a model system for potential human gene therapy. In these studies, we have demonstrated transduction and expression of the human MDR gene using ecotropic and amphotropic MDR-retroviral producer lines. To obtain more mouse hematopoietic cells for detailed study, mouse fetal liver cells (FLC) have been used for MDR transduction and expression, and to reconstitute the ablated marrows of live adult mice. FLC contain hematopoietic cells that have a reconstituting capacity comparable to that of adult mouse bone marrow cells. However, to our surprise, FLC can only be transduced with ecotropic retrovirus and not with amphotropic virus. This restriction of transduction of FLC cannot be overcome by higher titer virus. The resistance to amphotropic transduction by FLC may be part of a changing developmental program that results in a different antigen repertoire on FLC as compared with adult bone marrow cells.

Animals↗