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PubMed2004

Development of an efficient method for the isolation of factors involved in gene transcription during rice embryo development.

Summary An efficient yeast-based system was developed for the isolation of plant cDNAs encoding transcription factors (TFs) and proteins with transcription activation functions (co-activators). The system consists of two vectors: (i) a reporter vector (pG221) harboring the iso-1-cytochrome c (CYC1) core promoter and the beta-galactosidase (lacZ) gene; and (ii) a cDNA library construction vector (pYF503), which yields a library of plant peptides fused to the GAL4-binding domain (GAL4-BD). Expression of a peptide harboring the characteristics of a transcriptional activator leads to expression of lacZ, allowing for selection of relevant colonies. TFs during rice embryo development were isolated through this system. Approximately 200 confirmed positive colonies were obtained from screening 10(6) yeast colonies, and sequence analysis of conserved domains identified 75 independent cDNAs, 20 of which encoded plant TFs or co-activators, including members of the APETALA2 (AP2)/ethylene-responsive element-binding protein (EREBP), MYB and growth-regulating factor (GRF) families. Peptides encoded by 13 of the isolated cDNAs were classified as potential TFs or co-activators because of the presence of conserved TF-like domains. Additionally, 2, 11, and 13 clones encoded kinases, chromosome-related proteins, and unknown proteins, respectively, while the remaining 16 cDNAs were associated with specific functions seemingly unrelated to TFs. Expression pattern analysis of selected TF-encoding genes via RT-PCR revealed that these genes were expressed during seed development, with differential transcription observed during various stages. This work provides informative hints for further study of the regulatory mechanism of rice seed development and illustrates an identification strategy that will be of practical value for the isolation of TFs and co-activators associated with specific plant developmental processes.

Amino Acid Sequence↗

PubMed1987

Development of enzymic zonation in liver parenchyma is related to development of acinar architecture.

The appearance of the distribution patterns of the NH3-metabolizing enzymes carbamoylphosphate synthetase, glutamate dehydrogenase, and glutamine synthetase in the developing liver of an altricial species (rat) was compared with that in the developing liver of a closely related, precocial species (spiny mouse). The comparison showed that the development of hepatic acinar architecture, rather than perinatal adaptation, is responsible for the development of periportal and pericentral compartments of gene expression. Conditions that confine the expression of specific enzymes to the pericentral compartment of the acinus originate before conditions that confine the expression of (other) specific enzymes to the periportal compartment. However, whether or not the site of gene expression is restricted to specific compartments within the liver acinus, the rate of expression of the gene involved can also be adaptively regulated. Therefore, different factors appear to control the site and the rate of gene expression within one tissue.

Aging↗

PubMed1992

Early heart development in the chick embryo: effects of isotretinoin on cell proliferation, alpha-actin synthesis, and development of contractions.

Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. Though very effective, it is teratogenic if administered during pregnancy, and its teratogenic effect may be related to the normal activity of retinoids as signalling molecules in the embryo. Although its exact mechanism of action is unknown, it has been suggested that it causes its characteristic pattern of defects that includes heart defects, by inhibiting the migration of neural crest cells. However, other effects on cells are known. We studied early cardiac cell proliferation using incorporation of bromodeoxyuridine (BrdU) and detection with a monoclonal anti-BrdU. Proliferation in heart tissue of whole embryo cultures was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level in myocardium. We studied its effects in culture on precardiac explant development in the absence of the neural crests. Culture of precardiac mesodermal-endodermal explants revealed that development of heart vesicles from the mesoderm was little affected, but the development of heartbeat was inhibited depending on dose in the 10(-5) to 10(-7) M range. The effect on development of contractions was augmented in the presence of serum; it could be duplicated by all-trans-retinoic acid, and it was reversible. Synthesis of the alpha-actin isotype, analyzed by isoelectric focusing, was found to be inhibited or delayed. The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis.

Actins↗

PubMed2004

Somite development without influence of the surface ectoderm in the chick embryo: the compartments of a somite responsible for distal rib development.

In the development of the somite, signals from neighboring tissues have been suggested to play critical roles. We have found that when interaction between the ectoderm and the somite is blocked by inserting a piece of polyethylene terephatalate film between them in 2-day-chicken embryo, one of the derivatives of somite, the distal rib, did not form. We examined somite development after the operation, to know the correlation between somite development and distal rib formation. In the operated embryo, the dermomyotome was medio-laterally shorter than in the normal embryo, and Pax3 and Sim1 expressions that are seen in the lateral part of normal dermomyotomes were not found, suggesting that the lateral part of the dermomyotome was missing. Although the sclerotome appeared to be normal in its histology and Pax1 expression pattern in the operated embryo, we could not detect the expression of either Scleraxis nor gamma-FBP that are expressed in the cells around the boundaries between the adjacent dermomyotomes in normal embryos. Thus, under the influence of surface ectoderm, the lateral part of dermomyotome and/or the mesenchyme around rostral and caudal edges of dermomyotomes are suggested to play an important role in the distal rib development.

Animals↗

PubMed1967

Health, population, and economic development. International health programs have an important role in promoting economic development and population control.

Health as a basic human value is particularly important to people in the developing world. Rates of economic development lower than had been hoped for and ever more steeply rising population growth have precipitated a reaction against public health programs. Among economists, agriculturalists, and even health professionals the philosophy arose that one should "hold back" on using modern weapons against disease because they are "too effective." To satisfy the recognized popular demand, simple and relatively ineffective measures of curative medicine could be substituted. It was said that the emphasis should be, instead, on agriculture, community development, education, and industrialization and that family planning should be pushed as a separate program. Documentation presented here sharply challenges such a point of view. No segment of the total development process can be effective without the other sectors.

Demography↗

PubMed2002

In siblings with similar genetic susceptibility for inflammatory bowel disease, smokers tend to develop Crohn's disease and non-smokers develop ulcerative colitis.

BACKGROUND AND AIMS: Smoking tobacco has opposite effects on the different forms of inflammatory bowel disease (IBD). It predisposes to the development of Crohn's disease (CD) yet is associated with a reduced incidence of ulcerative colitis (UC). We have studied sib pairs discordant for both smoking and IBD phenotype (UC or CD) to investigate whether smoking determines the type of IBD that develops in individuals with very similar genetic susceptibility. PATIENTS: Smoking habits and disease characteristics were analysed in 242 IBD pedigrees (658 patients). Within this group there were 339 affected sibling pairs of whom 89 were discordant for smoking when diagnosed. RESULTS: Smoking at diagnosis was associated with development of CD (odds ratio (OR) 3.55; 95% confidence limits 2.50-5.02; p<0.001) in all of the familial patients, with increases when analysed for ileocaecal disease, fibrostenosis, and intestinal resection. Smokers were also protected from UC (OR 0.28; 0.2-0.4; p<0.001). Of 89 sibling pairs discordant for smoking at diagnosis, 23 were also discordant for disease type-in 21 of these, CD occurred in the smoker and UC in the non-smoker (OR 10.5; 2.6-92; p<0.0001). CONCLUSIONS: Smoking is a strong environmental risk factor for Crohn's disease and increases the likelihood of needing surgery. However, sib pairs who are discordant for both smoking and IBD type almost always show CD in the smoker and UC in the non-smoker, and so in some cases tobacco consumption acts on IBD genetic predisposition to shift the phenotype from UC towards CD. The explanation of part of the apparent "protective" effect of smoking on sporadic UC may be that the form of IBD that develops in a proportion of smokers is not UC but CD.

Adult↗

PubMedDate not supplied

Effect of long-term noise exposure on the developing and developed ear in the Rat.

There have been reports that the developing ear is more sensitive than the adult ear to noise-induced hearing loss. This was investigated by testing auditory function in rats, both electrophysiologically and histologically, following exposure to broad-band noise (12 h/day for 15 days) at different stages of auditory development (neonates and adults), and also in age-matched controls. An exposure of 90 dB SPL broad-band noise caused no long-term change in auditory function in either age group. A higher exposure (102 dB SPL) caused greater long-term changes in hearing in the adult compared to the young noise-exposed rats, although histology showed greater damage to hair cells in the younger animals. Therefore, functionally, the developing ear does not seem more vulnerable than the developed ear to acoustic trauma.

Age Factors↗

PubMed2001

Study on concretions developed around urinary catheters and mechanisms of renal calculi development.

AIMS: To study the structure and composition of encrustation and concretions developed on urinary catheters to better understand their formation mechanism to be able to prevent them. METHODS: The surface of catheters was studied by direct and scanning electron microscopy observation. In vitro formation of encrustations was performed in synthetic urine. RESULTS: The surface of catheters was covered by a continuous layer of organic matter, on which a thin scale consisting of crystals of calcium oxalate monohydrate (COM), uric acid anhydrous or calcium phosphate developed. Encrustations observed on catheters generally exhibited the same composition as the previously developed renal calculi. In catheters collected from patients without previous episodes of renal calculi or with previous episodes of infected renal calculi in which infection was afterwards eradicated, on the first organic layer, in that case plate-like COM crystals forming a columnar layer were observed. In vitro experiments demonstrated that COM columnar structures were only formed when normocalciuric urine containing organic matter was used, and the presence of crystallization inhibitors, as phytate, notably delayed their formation. CONCLUSION: Calcium oxalate was the main crystalline phase developed on catheters inserted in patients, specially in the absence of urinary infection or urinary pH values <5.5 and high urinary uric acid levels. Thus, prophylaxis of encrustations may consist of preventive measures usually applied in cases of recurrent idiopathic calcium oxalate urolithiasis.

Adult↗

PubMed1979

Development and aging of cholinergic synapses. I. Endogenous levels of acetylcholine and choline in developing autonomic ganglia and iris of the chick.

Acetylcholine (ACh) and choline (Ch) levels were measured by means of a sensitive micromethod in developing irises, ciliary and sympathetic ganglia of the chick, starting at 5--7 days of incubation (DI) up to 1 year of age. The neurotransmitter is present in all three organs at relatively low levels (1--10 pmol) from 5 DI (iris) or 7 DI (ciliary and sympathetic ganglion). This is followed by a rapid and sustained 9-fold increase in all three tissues up to 14 DI. Thus, it appears that low levels of ACh may be sufficient for neurotransmission to occur in the primitive ciliary ganglion and iris. After hatching, total ACh levels continue to increase up to 1 year of age in the iris and ciliary ganglion and up to 3 months in the sympathetic ganglion. The increase may depend on either an increased functional demand for the neurotransmitter or an increased number of preganglionic terminals. In general Ch levels parallel closely the levels of ACh in each organ throughout development. It is concluded that ACh and Ch are present since the earliest detectable stages of development in the ganglia and iris, and their first increase seems to be correlated to the phase of innervation of the organs. The subsequent increase probably correlates to synaptogenesis. The close relationship between Ch and ACh levels indicates a regulatory role of Ch for ACh synthesis during neuronal development.

Acetylcholine↗

PubMed2003

Inhibition of hydroxymethylglutaryl-coenzyme a reductase reduces Th1 development and promotes Th2 development.

Several prospective clinical studies have indicated that hydroxymethylglutaryl-coenzyme A reductase inhibitors, statins, prevent cardiovascular events in part through their antiinflammatory properties. Because inflammation is positively and negatively regulated by T helper (Th) 1 cells and Th2 cells, respectively, we examined the effects of statins on the Th polarization in vitro and in vivo. Here we demonstrated that the statins tested, ie, cerivastatin, simvastatin, lovastatin, and atorvastatin, promoted Th2 polarization through both inhibition of Th1 development and augmentation of Th2 development of CD4+ T cells primed in vitro with anti-CD3 antibody and splenic antigen-presenting cells. Cerivastatin exerted most potent effect on modulation of Th1/Th2 development, and the effect was completely abrogated by an addition of mevalonate. Consistent with in vitro experiments, cerivastatin treatment decreased IFN-gamma production of lymph node cells from mice immunized with ovalbumin emulsified in complete Freund's adjuvant, indicating that Th1 development is also suppressed in an in vivo proinflammatory environment. In this murine model, cerivastatin significantly reduced mesangial matrix expansion of glomeruli in the kidney and attenuated proteinuria. The decrease of glomerular sclerosis by cerivastatin treatment was positively related to the suppression of interferon (IFN)-gamma-producing Th1 response in draining lymph node cells. Hence, these findings strongly suggest that statins' inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase regulates Th1/Th2 polarization in vivo and such a mechanism possibly plays a pathophysiological role in immune-related glomerular injury.

Animals↗

PubMed2000

Preoperative MRA flow quantification in CEA patients: flow differences between patients who develop cerebral ischemia and patients who do not develop cerebral ischemia during cross-clamping of the carotid artery.

BACKGROUND AND PURPOSE: We sought to investigate whether preoperative volume flow in the internal carotid arteries (ICAs), the basilar artery (BA), and the middle cerebral arteries (MCAs) and collateral flow via the circle of Willis differ between patients who do and patients who do not develop cerebral ischemia during clamping of the carotid artery in carotid endarterectomy (CEA). METHODS: Quantitative volume flow in the ICAs, BA, and MCAs and directional flow in the circle of Willis were measured preoperatively with 2-dimensional phase-contrast MR angiography in 86 CEA patients. During the operation, electroencephalographic (EEG) recordings were obtained that were monitored by a clinical neurophysiologist. Reference volume flow values were assessed in 24 control subjects. RESULTS: In patients with an ICA stenosis without contralateral ICA occlusion (n=62), of whom 16% developed ischemic EEG changes during clamping, preoperative flow in the clamped ICA was significantly higher in patients with cerebral ischemia than in patients without (mean, 278 versus 160 mL/min; P:<0.05). Flow in the contralateral ICA (156 versus 273 mL/min; P:<0.01), flow in the BA (116 versus 165 mL/min; P:<0.05), and presence of collateral flow via the circle of Willis to the clamped ICA (0% versus 37%; P:<0.05) were significantly lower. MCA flow did not differ significantly between groups. Additionally, in patients with an ICA stenosis and a contralateral ICA occlusion (n=24), of whom 42% developed cerebral ischemia, preoperative flow in the clamped ICA was significantly higher in patients with cerebral ischemia than in patients without (309 versus 239 mL/min; P:<0.05). BA flow, MCA flow, and presence of willisian collateral flow (0% versus 14%) did not differ significantly between groups. CONCLUSIONS: Preoperative volume flow in the clamped ICA is significantly higher in CEA patients with ischemic EEG changes during clamping than in CEA patients without such changes. The latter patients probably have better developed collateral pathways preoperatively.

Aged↗

PubMedDate not supplied

Evaluation of education program developments: illustration of the research and development cycle.

The Research and Development (R and D) cycle is a program development model used to translate research findings into educational programs or products ready for use in the field. The R and D cycle is illustrated by describing its application to Effective Patient Teaching, a course on teaching skills for health professionals. Evaluation is a continuing part of program development. Evaluation methods need not follow a rigid formula; methods will generally change with the stages of program development and the evaluation purposes.

Educational Measurement↗

PubMed1982

Macrocyst development in Dictyostelium discoideum. I. Induction of synchronous development by giant cells and biochemical analysis.

In Dictyostelium discoideum, cytological and physiological studies on macrocyst formation revealed that this process consists of at least two steps: the production of giant cells, which are believed to be formed from the fusion of cells of two opposite mating types, and the subsequent induction of macrocyst development by the giant cells. The conditions that had been considered formerly to be required for macrocyst formation, such as darkness at the presence of two cells of complementary mating types in heterothallic strains, were actually required only for the production of the giant cells. Once giant cells are produced, the surrounding cells can aggregate and form macrocysts even in the light. Furthermore, it was demonstrated that giant cells can switch the developmental mode of the surrounding cells to macrocyst formation. That is, if a critical number of the isolated giant cells are introduced into a cell population of a single strain of NC4, which normally would produce only fruiting-bodies, macrocysts are formed instead. When in the presence of giant cells, the development of macrocysts may be initiated by starvation. Therefore, if all cells are made to starve simultaneously development begins and proceeds synchronously. Using this technique of synchronous development, the developmental kinetics of enzyme activities were assayed during macrocyst and fruiting-body formation. Considerable differences in the patterns of those enzyme activities were demonstrated between the two developmental modes of D. discoideum.

Acetylglucosaminidase↗

PubMed2003

Ovarian development in intrauterine growth-retarded and normally developed piglets originating from the same litter.

Epidemiological studies in humans linking adult disease to growth in utero indicate that prenatal life is a critical period for the appropriate development of the reproductive axis. The aim of this study was to compare ovarian development in intrauterine growth-retarded and normally grown piglets originating from the same litter. Intrauterine growth-retarded piglets (runts) were identified on the basis of statistical analysis of the birth weight distribution within each litter. At birth, ovaries were collected from runt piglets (n=14) and their respective mean weight (normal, n=14) littermates. Ovaries were weighed and fixed, and development of ovarian germ cells was quantified in haematoxylin-eosin-stained paraffin wax sections using an image analysis system. Germ cell loss, using an in situ TdT-mediated dUTP nick-end labelling (TUNEL) assay for DNA fragmentation, and follicle cell activity, using immunohistochemistry to demonstrate vimentin, were studied in ovarian sections. At birth, body weight and absolute ovarian mass were significantly lower in runt piglets compared with their respective normally grown littermates (body weight: 733+/-38.5 versus 1530+/-39.7 g; ovarian mass: 51+/-3.0 versus 108+/-9.6 mg; P<0.001 for both). In the ovary, the proportion of nests of oogonia, the number of oocytes and TUNEL-positive cells, and the localization and intensity of vimentin immunoreactivity were not different between runt and normal littermates. However, runt piglets had more primordial follicles (268+/-18.6 versus 235+/-20.1 per mm(2) of cortex; P<0.05), fewer primary follicles (11+/-2.0 versus 20+/-3.0 per mm(2) of cortex; P<0.001) and no secondary follicles compared with normal piglets. These findings indicate that intrauterine growth retardation delayed follicular development in pig ovaries at birth.

Animals↗

PubMed2002

Safety evaluation and drug development based on biological fate of drugs -efforts made to overcome drug interaction in drug development-.

1. Assay methods to detect drug interaction in toxicological samples were established by determining cytochrome P450 content and its activity in liver samples. The O-dealkylation reaction of 7-alkoxycoumarin was indicated to reflect changes in the molecular forms of P450s, and the enzyme induction or inhibition in the toxicological samples was easily detected by using the established methods. 2. During toxicological studies of 450191-S or the sleep inducer rilmazafone, a phenobarbital type-induction of hepatic drug metabolizing enzymes was observed in animals, and the doses required for the induction differed markedly between rats and dogs. Enzyme induction was caused by some specific metabolites of 450191-S, and the plasma concentrations of these metabolites were comparable when the enzyme induction was developed in both animals. 3. A nonsteroidal antiinflammatory compound 480156-S showed a slight or no effect on microsomal drug metabolizing activity in rats. On the other hand, repeated administration of this compound to humans resulted in a marked decrease in the oxidative metabolism of 480156-S, followed by a marked increase in the plasma concentrations of the compound. When volunteers were given 480156-S followed by several drugs, such as tolubutamide, the plasma clearance was delayed remarkably, indicating a severe drug interaction. 4. Cytochrome P450 belonging to the CYP2C family was indicated to participate in the oxidative metabolism of 480156-S in both rat and human liver microsomes. The preincubation of microsomes with 480156-S caused a concentration-dependent inhibition of CYP2C-dependent tolubutamide hydroxylation reaction in both rats and humans. There was a marked species difference in the susceptibility to the inhibitory effect of 480156-S, and the concentration required to inhibit rat CYP2C was almost 10 times higher than that required in humans. 5. The cephem antibiotics having N-methyltetrazolethiol (NMTT) at the 3'-position substituent were demonstrated to inhibit mitochondrial low K(m) aldehyde dehydrogenase (ALDH), and produced disulfiram-like (Antabuse) reaction during alcohol metabolism. Pharmacokinetic studies indicated that NMTT released from the antibiotics in bile duct or intestine cause the inhibitory action followed by the development of disulfiram-like reaction. 6. Attempts had been made to develop new cephem antibiotics lacking the disulfiram-like reaction by changing the chemical structure of 3'-position substituents, and a hydroxyethyltetrazolethiol was found not to inhibit the enzyme. Based on this result, together with the antibacterial activity, we have developed a new oxacephem antibiotic flomoxef (6315-S). Flomoxef showed no disulfiram-like reaction both in rats and human.

Journal Article↗

PubMed1975

Moral development and perceptual role-taking egocentrism: their development and interrelationship across the life-span.

Moral judgments and perceptual role taking egocentrism were assessed in seventy-two middle-class people whose age range encompassed a significant portion of the life span. Findings support the anticipated curvilinear relationship between moral development and age, and egocentrism and age. However, the close conceptual development and age, and egocentrism and age. However, the close conceptual relationship between moral development and egocentrism throughout life received only slight statistical support, which attained significance only in the fifteen- to nineteen-year-old age group. The existence of "self-involving" egocentrism was postulated to be an important determinant or moral development during adulthood.

Adolescent↗

PubMed1995

Human prenatal craniofacial development related to brain development under normal and pathologic conditions.

A survey is given of current knowledge of the interrelationship between facial, cranial and brain development in humans. First, normal facial, cranial (mandible, maxilla, palatine bone, cranial base, theca cranii, dentition), and brain development are described separately. Then, developmental interrelationships are illustrated under normal and pathologic conditions (cleft lip and palate, holoprosencephaly, anencephaly, amniotic band sequence). New observations are described in detail, and references are given to previously published articles. A close interconnection exists between the development of the face, the craniofacial skeleton, and the brain. This is illustrated by new observations in cleft palate fetuses and new theories about the etiology of holoprosencephaly and tooth agenesis. The survey focuses, moreover, on the importance of the face and the cranial base in endocrine development. Borderlines between face regions and cranial regions with different developmental origin are set up for future elucidation of the etiology behind syndromes involving the craniofacial regions.

Amniotic Band Syndrome↗

PubMed1991

Development of multipotential haemopoietic stem cells to neutrophils is associated with increased expression of receptors for granulocyte macrophage colony-stimulating factor: altered biological responses to GM-CSF during development.

Interleukin-3 (IL-3) dependent multipotent haemopoietic stem cells FDCP-Mix A4 (A4) were induced to differentiate and develop into mature neutrophils in response to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) plus granulocyte CSF (G-CSF). This resulted in an increase in cell number over seven days of culture, following which the cells lost the ability to undergo further proliferation. The effect of GM-CSF on these cells has been assessed at various stages of development. Clonogenic cells, able to respond to GM-CSF, were generated only at days 3, 4 post-induction. From day 5 onwards, mature post-mitotic neutrophils are produced and clonogenic cells are lost. Loss of proliferative potential, in response to GM-CSF, was confirmed using [3H]-thymidine incorporation. Receptors for GM-CSF, were also measured during development using [125I]-GM-CSF binding assays. Although the dissociation constant for GM-CSF binding sites did not vary considerably, the number of such sites increased dramatically from about 20 (day 0, when the cells have a primitive morphology) to about 1000 by day 6 (when the cells are predominantly mature neutrophils). GM-CSF-stimulated Na+/H+ antiport activation was also determined. Although few GM-CSF receptors are expressed at day 0, there is a significant response (63% of maximal) to GM-CSF in terms of intracellular alkalinisation: this response increased markedly until, by day 4 (700 GM-CSF binding sites/cell), there is a maximal activation of the antiport by GM-CSF. By day 7 (greater than 900 GM-CSF binding sites/cell), however, there is significant reduction in activation of the Na+/H+ antiport by GM-CSF. Nonetheless, increased viability of these mature cells is still seen in response to GM-CSF. These results suggest that not only does expression of GM-CSF receptors alter during development of multipotential cells to mature neutrophils, but that these receptors are coupled to different intracellular effector mechanisms as the cells progressively mature.

Cell Differentiation↗