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Gastric lipase and pepsin activities in the developing ferret: nonparallel development of the two gastric digestive enzymes.

BACKGROUND: Gastric lipase has an important compensatory function in neonatal fat digestion. The activity level of pepsin and its role in protein digestion is less well understood. We have, therefore, studied the ontogeny of lipase and pepsin in the ferret, a species with a neonatal fat digestion pattern similar to that of humans. METHODS: Gastric lipase and pepsin activities were quantified from the late fetal period throughout lactation, and were compared with those of the adult. RESULTS: The data show earlier ontogeny and much more rapid rise of lipase activity than of pepsin. Lipase activity was present during the last week of fetal development, whereas pepsin was detected only postnatally. Lipase activity was 72.8% +/- 14.2% and 153% +/- 9.95% and pepsin activity was 11.6% +/- 1.3% and 30.1% +/- 1.3% of the adult level at 2 and 4 wk of age, respectively. CONCLUSIONS: We conclude that lipase activity develops early and exceeds adult activity during the suckling period, when fat intake is very high. The low pepsin activity and high postprandial pH probably limit gastric proteolysis, thereby contributing to the structural and functional stability of milk proteins, many with protective or bioactive function in the gastrointestinal tract of the newborn.

Animals↗

Water deficit and spatial pattern of leaf development. Variability In responses can Be simulated using a simple model of leaf development

We analyzed the effect of short-term water deficits at different periods of sunflower (Helianthus annuus L.) leaf development on the spatial and temporal patterns of tissue expansion and epidermal cell division. Six water-deficit periods were imposed with similar and constant values of soil water content, predawn leaf water potential and [ABA] in the xylem sap, and with negligible reduction of the rate of photosynthesis. Water deficit did not affect the duration of expansion and division. Regardless of their timing, deficits reduced relative expansion rate by 36% and relative cell division rate by 39% (cells blocked at the G0-G1 phase) in all positions within the leaf. However, reductions in final leaf area and cell number in a given zone of the leaf largely differed with the timing of deficit, with a maximum effect for earliest deficits. Individual cell area was only affected during the periods when division slowed down. These behaviors could be simulated in all leaf zones and for all timings by assuming that water deficit affects relative cell division rate and relative expansion rate independently, and that leaf development in each zone follows a stable three-phase pattern in which duration of each phase is stable if expressed in thermal time (C. Granier and F. Tardieu [1998b] Plant Cell Environ 21: 695-703).

Journal Article↗

Water Relations of Seed Development and Germination in Muskmelon (Cucumis melo L.) : I. Water Relations of Seed and Fruit Development.

Total water potential (psi), solute potential, and turgor potential of field-grown muskmelon (Cucumis melo L.) fruit tissue (pericarp) and seeds were determined by thermocouple psychrometry at 5-day intervals from 10 to 65 days after anthesis (DAA). Fruit maturity occurred between 44 and 49 DAA, and seed germination ability developed between 35 and 45 DAA. Pericarp psi was essentially constant at approximately -0.75 megapascal (MPa) from 10 to 25 DAA, then decreased to a minimum value of -1.89 MPa at 50 DAA before increasing to -1.58 MPa at 65 DAA. Seed psi remained relatively constant at approximately -0.5 MPa from 10 to 30 DAA then decreased to -2.26 MPa at 50 to 60 DAA before increasing to -2.01 MPa at 65 DAA. After a rapid increase to 20 DAA, seed fresh weight declined until 30 DAA due to net water loss, despite continuing dry weight gain. As fruit and seed growth rates decreased, turgor potential initially increased, then declined to small values when growth ceased. A disequilibrium in psi was measured between seeds and pericarp both early and late in development. From 20 to 40 DAA, the psi gradient was from the seed to the tissue, coinciding with water loss from the seeds. From 50 to 65 DAA, seed psi decreased, causing a reversal of the psi gradient and a slight increase in seed water content. The partitioning of solutes between symplast and apoplast may create and maintain psi gradients between the pericarp and seed. The low solute potential within the pericarp due to solute accumulation and loss of cellular compartmentation during ripening and sensecence may be involved in prevention of precocious germination of mature seeds.

Journal Article↗

Water Relations of Seed Development and Germination in Muskmelon (Cucumis melo L.) : IV. Characteristics of the Perisperm during Seed Development.

We previously reported that an apparent water potential disequilibrium is maintained late in muskmelon (Cucumis melo L.) seed development between the embryo and the surrounding fruit tissue (mesocarp). To further investigate the basis of this phenomenon, the permeability characteristics of the tissues surrounding muskmelon embryos (the mucilaginous endocarp, the testa, a 2- to 4-cell-layered perisperm and a single cell layer of endosperm) were examined from 20 to 65 days after anthesis (DAA). Water passes readily through the perisperm envelope (endosperm + perisperm), testa, and endocarp at all stages of development. Electrolyte leakage (conductivity of imbibition solutions) of individual intact seeds, decoated seeds (testa removed), and embryos (testa and perisperm envelope removed) was measured during imbibition of freshly harvested seeds. The testa accounted for up to 80% of the total electrolyte leakage. Leakage from decoated seeds fell by 8- to 10-fold between 25 and 45 DAA. Presence of the perisperm envelope prior to 40 DAA had little effect on leakage, while in more mature seeds, it reduced leakage by 2- to 3-fold. In mature seeds, freezing, soaking in methanol, autoclaving, accelerated aging, and other treatments which killed the embryos had little effect on leakage of intact or decoated seeds, but caused osmotic swelling of the perisperm envelope due to the leakage of solutes from the embryo into the space between the embryo and perisperm. The semipermeability of the perisperm envelope of mature seeds did not depend upon cellular viability or lipid membrane integrity. After maximum seed dry weight is attained (35-40 DAA), the perisperm envelope prevents the diffusion of solutes, but not of water, between the embryo and the surrounding testa, endocarp, and mesocarp tissue.

Journal Article↗

The development of a provincial radiation oncology service: the first year report and its implications for future developments.

This study compares the actual first year's workload of a new radiation oncology department with that predicted, and assesses the impact of the differences, and their implications for future similar developments. The treatment records and diaries for the Geelong Hospital Radiation Oncology Department were reviewed after the first 12 months of operation (opened in June 1992). Statistics relating to the number of patients seen, number treated, diagnosis, etc., were evaluated and compared to the original estimates based upon population statistics and likely referral rates. Nine hundred and seven new patients were seen in this period, and from them 718 courses of treatment were initiated. One hundred and eighty-nine cases (20% of referrals) were seen but not treated. A further 102 treatment courses (14% of total) were initiated upon patients who had previously been irradiated. Forty-six per cent of patients were managed by 10 fractions or fewer, and a further 23% by 25 or more fractions. Eighty per cent of patients were managed by one or two fields. Electrons were used in only 14% of cases. Further calculations suggested a further possible 441 cases of referral could be expected, based upon current population statistics. Referral rates for radiation oncology are highly dependent on a number of factors. As a result, estimates of referrals and hence the size of a department required for a given population vary widely. Our data support these concepts, and the concept that referral is also strongly dependent upon the distance patients need to travel. In considering the development of units outside of major cities it is suggested that referrals are likely to be on the high side of estimates and a minimum two-machine unit is essential to cover the given workload.

Female↗

Characterization of TROY-expressing cells in the developing and postnatal CNS: the possible role in neuronal and glial cell development.

A member of the tumor necrosis factor receptor superfamily, TROY, is expressed in the CNS of embryonic and adult mice. In the present study, we characterized TROY-expressing cells in the embryonic and postnatal forebrain. In the early embryonic forebrain, TROY was highly expressed in nestin-positive neuroepithelial cells and radial glial cells, but not in microtubule-associated protein 2-positive postmitotic neurons. During the late embryonic and postnatal development, expression of TROY was observed in radial glial cells and astrocytes, whereas its expression was not detected in neuronal lineage cells. In addition, TROY was exclusively expressed in Musashi-1-positive multipotent/glial progenitors in the postnatal subventricular zone. To investigate the functions of TROY in neural development, we overexpressed TROY in PC12 cells and established stably expressing cell clones. As expected, the signals from overexpressed TROY were constitutively transduced via the activation of the nuclear factor-kappaB and the c-Jun N-terminal kinase pathways in such clones. In addition, upregulation of negative basic helix-loop-helix transcription factors, HES-5 and Id2 proteins, was observed in the TROY-overexpressing clones. Interestingly, the overexpression of TROY in PC12 cells strongly inhibited nerve growth factor-induced neurite outgrowth with reduction of some markers of differentiated neurons, such as neurofilament 150 kDa and neuron-specific beta-tubulin. These findings suggest that the signaling from TROY regulates neuronal differentiation at least in part.

Animals↗

Vitamin K--its essential role in craniofacial development. A review of the literature regarding vitamin K and craniofacial development.

The normal vitamin K status of the human embryo appears to be close to deficiency. Maternal dietary deficiency or use of a number of therapeutic drugs during pregnancy, may result in frank vitamin K deficiency in the embryo. First trimester deficiency results in maxillonasal hypoplasia in the neonate with subsequent facial and orthodontic implications. A rat model of the vitamin K deficiency embryopathy shows that the facial dysmorphology is preceded by uncontrolled calcification in the normally uncalcified nasal septal cartilage, and decreased longitudinal growth of the cartilage, resulting in maxillonasal hypoplasia. The developing septal cartilage is normally rich in the vitamin K-dependent protein matrix gla protein (MGP). It is proposed that functional MGP is necessary to maintain growing cartilage in a non-calcified state. Developing teeth contain both MGP and a second vitamin K-dependent protein, bone gla protein (BGP). It has been postulated that these proteins have a functional role in tooth mineralization. As yet this function has not been established and abnormalities in tooth formation have not been observed under conditions where BGP and MGP should be formed in a non-functional form.

1-Carboxyglutamic Acid↗

MR imaging of the developing human brain. Part 1. Prenatal development.

To establish a baseline of the magnetic resonance (MR) imaging appearance of the fetal brain in early stages of development, the authors undertook a study of fixed and fresh specimens of embryos and fetuses of 6-28 weeks gestational age. Images of formalin-preserved and fresh specimens were comparable in their depiction of anatomic structures. On MR images of embryos of 6 weeks gestational age, the rhombic and cervical flexures, aqueduct of Sylvius, diencephalon, cerebellum, cerebral hemisphere, and fourth ventricle could be differentiated. The optic recess and chiasm, pituitary gland, pineal recess, third ventricle, pons, olfactory lobe, corpus striatum, insula, and parietal and temporal lobes could be distinguished as early as 11 weeks gestation. Although MR imaging is impractical as a screening tool for intrauterine abnormalities, it can demonstrate the fetus in great detail and allows a more specific evaluation of fetal anatomy. With the information provided by MR imaging, it may be possible to establish guidelines for assessment of the stage of development during intrauterine life.

Brain↗

Detection of chronic kidney disease in patients with or at increased risk of cardiovascular disease: a science advisory from the American Heart Association Kidney And Cardiovascular Disease Council; the Councils on High Blood Pressure Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: developed in collaboration with the National Kidney Foundation.

Chronic kidney disease (CKD) occurs commonly in patients with cardiovascular disease. In addition, CKD is a risk factor for the development and progression of cardiovascular disease. In this advisory, we present recommendations for the detection of CKD in patients with cardiovascular disease. CKD can be reliably detected with the combined use of the Modification of Diet in Renal Disease equation to estimate glomerular filtration rate and a sensitive test to detect microalbuminuria. All patients with cardiovascular disease should be screened for evidence of kidney disease with these two determinations.

American Hospital Association↗

Development of an in vitro test battery for the estimation of acute human systemic toxicity: An outline of the EDIT project. Evaluation-guided Development of New In Vitro Test Batteries.

The aim of the Evaluation-guided Development of new In Vitro Test Batteries (EDIT) multicentre programme is to establish and validate in vitro tests relevant to toxicokinetics and for organ-specific toxicity, to be incorporated into optimal test batteries for the estimation of human acute systemic toxicity. The scientific basis of EDIT is the good prediction of human acute toxicity obtained with three human cell line tests (R(2) = 0.77), in the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme. However, the results from the MEIC study indicated that at least two other types of in vitro test ought to be added to the existing test battery to improve the prediction of human acute systemic toxicity - to determine key kinetic events (such as biotransformation and passage through biological barriers), and to predict crucial organ-specific mechanisms not covered by the tests in the MEIC battery. The EDIT programme will be a case-by-case project, but the establishment and validation of new tests will be carried through by a common, step-wise procedure. The Scientific Committee of the EDIT programme defines the need for a specific set of toxicity or toxicokinetic data. Laboratories are then invited to perform the defined tests in order to provide the "missing" data for the EDIT reference chemicals. The results obtained will be evaluated against the MEMO (the MEIC Monograph programme) database, i.e. against human acute systemic lethal and toxicity data. The aim of the round-table discussions at the 19th Scandinavian Society for Cell Toxicology (SSCT) workshop, held in Ringsted, Denmark on 6-9 September 2001, was to identify which tests are the most important for inclusion in the MEIC battery, i.e. which types of tests the EDIT programme should focus on. It was proposed that it is important to include in vitro methods for various kinetic events, such as biotransformation, absorption in the gut, passage across the blood-brain barrier, distribution volumes, protein binding, and renal clearance/accumulation. Models for target organ toxicity were also discussed. Because several of the outlier chemicals (paracetamol, digoxin, malathion, nicotine, paraquat, atropine and potassium cyanide) in the MEIC in vivo-in vitro evaluation have a neurotoxic potential, it was proposed that the development within the EDIT target organ programme should initially be focused on the nervous system.

Biotransformation↗

Developing a bioterrorism preparedness campaign for veterans: Using focus groups to inform materials development.

In the context of a global war on terrorism experts have focused on the potential for a bioterrorist incident to cause widespread health and psychological consequences. Preparation is critical to improving the U.S. response to future bioterrorist incidents and educating the public is recognized as a vital part of this preparedness effort. Under a grant from the U.S. Veterans Health Administration (VHA), researchers from a network of VA health care and research facilities initiated a program to develop and evaluate educational materials for veterans--including those with mental illness. This article describes the results of a series of focus groups with three veteran subpopulations of interest to characterize their concerns and information needs and summarizes the insights gained that helped guide materials development.

Bioterrorism↗

Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor.

Clinical trials of thrombopoietin (TPO), the central regulator of megakaryocytopoiesis, have revealed few side effects associated with its use. We here report a case of pancytopenia associated with the development of neutralizing antibodies to TPO that occurred in a patient who had undergone multicycle chemotherapy with multiple cycles of subcutaneous administration of pegylated recombinant human megakaryocyte growth and development factor. Samples of the patient's bone marrow showed trilineage hypoplasia with absence of myeloid, erythroid, and megakaryocyte progenitor cells but with elevated endogenous levels of erythropoietin, granulocyte colony-stimulating factor, and stem-cell factor. To our knowledge, this is the first report of an aplastic anemia-like syndrome associated with neutralizing antibodies to TPO.

Adenocarcinoma↗

Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics.

Although dietary, genetic, or disease-related excesses in urate production may contribute to hyperuricemia, impaired renal excretion of uric acid is the dominant cause of hyperuricemia in the majority of patients with gout. The aims of this review are to highlight exciting and clinically pertinent advances in our understanding of how uric acid is reabsorbed by the kidney under the regulation of urate transporter (URAT)1 and other recently identified urate transporters; to discuss urate-lowering agents in clinical development; and to summarize the limitations of currently available antihyperuricemic drugs. The use of uricosuric drugs to treat hyperuricemia in patients with gout is limited by prior urolothiasis or renal dysfunction. For this reason, our discussion focuses on the development of the novel xanthine oxidase inhibitor febuxostat and modified recombinant uricase preparations.

Carrier Proteins↗

Community participation in the treatment development process using community development teams.

Little literature exists about methods for adapting research-based treatments to typical practice settings. This report describes a 2-step process and associated methods used to adapt a school-based treatment program for middle-school youth with attention deficit hyperactivity disorder (ADHD) that operates in a controlled setting to one that can operate in a typical practice setting. Step 1 included a feasibility study that yielded important findings regarding potential obstacles to successful implementation. These data, along with original treatment manuals and literature on treatments for youth with ADHD, were utilized for Step 2--the Community Development Team (CDT) process. Data collected about the CDT process indicate that its strengths outweigh potential limitations. These methods are discussed in the context of successful collaborative procedures for developing and evaluating research-based treatments in practice settings.

Adolescent↗

Modulation of Erbb2 signaling during development: a threshold level of Erbb2 signaling is required for development.

We have generated a series of Erbb2 cDNA knock-in animals to explore the role of signaling pathways coupled to Erbb2 during development. Although this knock-in allele was hypomorphic, expressing tenfold less Erbb2 protein than wild type, the knock-in animals were healthy. However, a further twofold reduction in Erbb2 levels in hemizygous knock-in animals resulted in perinatal lethality with defects in the innervation of the diaphragm. Genetic rescue of this hypomorph was accomplished by expression of the Erbb2-Y1028F mutant in a comparable knock-in allele. Interestingly, hemizygous Y1028F animals were viable with normal innervation of the diaphragm. Molecular analyses revealed that the Y1028F allele expressed higher levels of Erbb2 and that Y1028 promoted the turnover of the receptor. In addition, ablation of the Shc-binding site in Erbb2 (Y1227) resulted in subtle defects in the sensory nerves not observed in the other mutant erbb2 strains. Thus, we have established how Erbb2 levels may be modulated through development and that a minimum threshold level of Erbb2 is required.

Animals↗

The development of an assay to detect mRNAs that affect early development.

We have constructed an assay to identify developmental effects of injected RNA molecules. The RNA is injected into the animal pole region of a 2- to 8-cell embryo. At the blastula stage, the animal cap is removed and its development in isolation tested. In controls, only epidermis is produced, but several of the injected RNA preparations, though not all, also form dorsal and ventral mesoderm and nervous tissue. This assay should be suitable for selecting cDNA clones complementary to mRNAs that direct development.

Animals↗

Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development.

The Drosophila sine oculis homeobox-containing gene is known to play an essential role in controlling the initial events of pattern formation in the eye disc and is also required for the development of other parts of the fly visual system including the optic lobes. In this paper, we report the isolation of a sequence-related gene referred to as Six3. Based on its amino acid sequence, this gene can be included in the new Six/sine oculis subclass of homeobox genes. Early on, Six3 expression is restricted to the anterior neural plate including areas that later will give rise to ectodermal and neural derivatives. Later, once the longitudinal axis of the brain bends, Six3 mRNA is also found in structures derived from the anterior neural plate: ectoderm of nasal cavity, olfactory placode and Rathke's pouch, and also the ventral forebrain including the region of the optic recess, hypothalamus and optic vesicles. Based on this expression pattern, we conclude that Six3 is one of the most anterior homeobox gene reported to date. The high sequence similarity of Six3 with the Drosophila sine oculis, and its expression during eye development, suggests that this gene is the likely murine homologue. This finding supports the idea that mammals and insects share control genes such as eyeless/Pax6 (Halder, G., Callaerts, P. and Gehring, W. J. (1995) Science 267, 1788-1792), and also possibly other members of the regulatory cascade required for eye morphogenesis. In Small eye (Pax6) mouse mutants Six3 expression is not affected. Finally, based on the chromosomal localization and the expression pattern of the mouse Six3 gene, the human Six3 cognate could be a good candidate to be at least one of the genes affected in patients with holoprosencephaly type 2 due to an interstitial deletion of 2p21-p22. This region shares a homology with the distal region of mouse chromosome 17 where Six3 has been mapped.

Amino Acid Sequence↗