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PubMed1998

Inhibitor development and substitution therapy in a developing country: Turkey.

Prevalence of inhibitor in developing countries, such as Turkey, where fresh frozen plasma (FFP) is still in use due to high cost of concentrates, is unknown. To determine the frequency of inhibitors in Turkish haemophiliacs exposed to blood products, 53 haemophilia A patients (age range 1-20; median: 11 years) and 12 haemophilia B patients (age range 3-20; median: 10 years), were evaluated; 31 haemophilia A patients (23 severe) received plasma-derived concentrates and 22 patients (10 severe) only FFP. No haemophilia B patients developed inhibitor, compared with seven of 53 (13%) haemophilia A patients, all with a severe defect (7/33; 21%) and treated with concentrates (7/23; 30%), whereas severe patients treated with FFP showed a lower risk to develop inhibitors (0/10, P = 0.07). Inhibitors were detected after 8-125 exposure days (median: 52). Intermediate-purity concentrates and pasteurization seemed to be linked with a higher risk of inhibitor compared to high-purity concentrates and solvent-detergent inactivation for seven patients with inhibitor. In four of seven inhibitor patients low-dose concentrate was administered at 25 IU kg-1 twice weekly and inhibitor disappeared in 1-4 months. This regimen might be recommended for immune tolerance in developing countries for its lower cost.

Adolescent↗
PubMed1996

Sucrose metabolism during cotyledon development of Vicia faba L. is controlled by the concerted action of both sucrose-phosphate synthase and sucrose synthase: expression patterns, metabolic regulation and implications for seed development.

The roles of sucrose-phosphate synthase (Sps) and sucrose synthase (Sus) in developing embryos of Vicia faba have been characterized. In the cotyledons the expression of both Sps and Sus is initiated in cells differentiating into storage tissue. This stage is characterized by a switch in the carbohydrate state from a high to a low hexoses to sucrose ratio. The carbohydrate state was found earlier to be controlled by seed coat-associated invertase. During cotyledon development the Sps-enzyme undergoes a cycle of deactivation and reactivation: the activated state is associated with the prestorage phase, desiccation and germination and the deactivated state with the storage phase. Sus activity is associated with the storage phase. Sps and Sus are differentially influenced by free sugars. Feeding hexoses to storage phase cotyledons increases levels of Sps-mRNA but not Sus-mRNA, Sps activity and Sps activation state and impairs storage functions evidenced by an increased sucrose to starch ratio and a downregulation of storage protein legumin B-mRNA. Sus enzyme activity is inhibited by free hexoses in vitro. It is proposed that the changing carbohydrate state during cotyledon development controls the ratio of Sps to Sus. Sps may have some significance for the initiation of the storage process possibly decreasing hexoses and/or increasing sucrose. The relevance of the changing carbohydrate state with respect to development and storage processes is discussed.

Base Sequence↗
PubMed2002

Tumorous shoot development (TSD) genes are required for co-ordinated plant shoot development.

This report describes the identification of novel plant genes that are required to ensure co-ordinated post-embryonic development. After germination the tumorous shoot development mutants of Arabidopsis thaliana develop disorganized tumorous tissue instead of organized leaves and stems. This results in green callus-like structures, which are capable of unlimited growth in vitro on hormone-free medium. The tsd mutants are recessive and belong to three complementation groups (tsd1, tsd2, tsd3). The genes were mapped to the bottom of chromosomes 5 and 1, and the top of chromosome 3, respectively. Histological analyses showed that the tsd mutants have different developmental defects. The shoot apical meristem of tsd1 formed only rudimentary leaves and was characterized by a degenerating L1 cell layer. tsd2 mutants had reduced cell adhesion and altered cell division planes in the L2 and L3 cell layers. The tumorous tissue of tsd3 mutants originated from the base of the leaf. Cytokinin levels that are inhibitory to the growth of wild-type seedlings bring about an enhanced growth response in all the tsd mutants. The steady state transcript levels of the histidine kinase CKI1 gene and the KNAT1 and STM homeobox genes were increased in tsd mutants, while mRNA levels of cell cycle genes were not altered. We hypothesize that the TSD gene products negatively regulate cytokinin-dependent meristematic activity during vegetative development of Arabidopsis.

Arabidopsis↗
PubMed2001

Development and implementation of a science training course for breast cancer activists: Project LEAD (leadership, education and advocacy development).

OBJECTIVE: To develop and implement Project LEAD (leadership, education, and advocacy development), a science course for breast cancer activists. POPULATION: Students were breast cancer activists and other consumers, mainly affiliated with advocacy organizations in the United States of America. SETTING: Project LEAD is offered by the National Breast Cancer Coalition; the course takes place over 5 days and is offered 4 times a year, in various cities in the United States of America. RESULTS: The Project LEAD curriculum has developed over 5 years to include lectures, problem-based study groups, case studies, interactive critical appraisal sessions, a seminar by an 'expert' scientist, role play, and homework components. A core faculty has been valuable for evaluating and revising the course and has proved necessary to provide consistent high quality teaching. Course evaluations indicated that students gained critical appraisal skills, enhanced their knowledge and developed confidence in selected areas of basic science and epidemiology. CONCLUSIONS: Project LEAD comprises a unique curriculum for training breast cancer activists in science and critical appraisal. Course evaluations indicate that students gain confidence and skills from the course.

Adult↗
PubMed2001

Regulating potential in development of a direct developing echinoid, Peronella japonica.

The regulating potential along the animal-vegetal axis of a direct developing echinoid, Peronella japonica, was investigated using LiCl. Animal caps isolated from 16-cell stage P. japonica embryos developed to permanent blastulae with an amniotic cavity. Treatment of animal caps with LiCl induced them to vegetalize with differentiation of the endoderm and subsequently develop into pluteus-like larvae. The larvae derived from the LiCl-treated animal caps were able to metamorphose and establish an adult body plan. A considerable fraction of whole embryos treated with LiCl exogastrulated and/or evaginated an amniotic cavity. The timing of the sensitivity to LiCl-mediated induction of evagination of the amniotic cavity was earlier than that for exogastrulation. Peronella japonica embryos became sensitive to LiCl induction of exogastrulation later than embryos of indirect developers. Some larvae with evaginated archenteron and/or evaginated amniotic cavity had metamorphic potential. These results suggest that LiCl can induce both vegetalization and evagination of invaginating structures. The present study is the first to show the potential of the presumptive ectoderm region to regulate the establishment of the adult body plan without any influence from other blastomeres, revealing that the regulating potential of sea urchin embryos is much larger than previously thought.

Animals↗
PubMed2001

Development of the arterial pattern in the upper limb of staged human embryos: normal development and anatomic variations.

A total of 112 human embryos (224 upper limbs) between stages 12 and 23 of development were examined. It was observed that formation of the arterial system in the upper limb takes place as a dual process. An initial capillary plexus appears from the dorsal aorta during stage 12 and develops at the same rate as the limb. At stage 13, the capillary plexus begins a maturation process involving the enlargement and differentiation of selected parts. This remodelling process starts in the aorta and continues in a proximal to distal sequence. By stage 15 the differentiation has reached the subclavian and axillary arteries, by stage 17 it has reached the brachial artery as far as the elbow, by stage 18 it has reached the forearm arteries except for the distal part of the radial, and finally by stage 21 the whole arterial pattern is present in its definitive morphology. This differentiation process parallels the development of the skeletal system chronologically. A number of arterial variations were observed, and classified as follows: superficial brachial (7.7%), accessory brachial (0.6%). brachioradial (14%), superficial brachioulnar (4.7%), superficial brachioulnoradial (0.7%), palmar pattern of the median (18.7%) and superficial brachiomedian (0.7%) arteries. They were observed in embryos belonging to stages 17-23 and were not related to a specific stage of development. Statistical comparison with the rates of variations reported in adults did not show significant differences. It is suggested that the variations arise through the persistence, enlargement and differentiation of parts of the initial network which would normally remain as capillaries or even regress.

Aorta↗
PubMed2002

Issues and barriers to development of clinically useful tumor markers: a development pathway proposal.

There are few tumor markers that are clinically useful in predicting therapeutic responses or patient outcomes despite nearly 20 years of advances in molecular biology. We discuss a variety of issues and barriers that have affected movement of clinical tests from research into clinical practice. Studies of new markers frequently lack clear hypotheses and are generally underpowered to reach statistically valid conclusions. Relevant clinical endpoints may not be possible to evaluate, often leading to suboptimal study designs. Major stumbling blocks exist because studies are rarely comparable. This makes it difficult to determine why results vary from study to study. It also prevents pooling of small datasets for analysis. We propose a tumor marker development pathway that we think will be more efficient and effective. The pathway depends on developing statistically valid study designs, focusing on assay refinement and standardization early in the process, including assay details in publications, and providing data in a format that allows comparison with other studies. The process described should be applicable to development of new technologies that include analysis and interpretation of large, complex datasets. The proposed marker development pathway will require thoughtful refinement and expansion, but it should begin a productive dialog.

Biomarkers, Tumor↗
PubMed2001

Early-generated preplate neurons in the developing telencephalon: inward migration into the developing striatum.

Specialized subsets of early-generated neurons provide the cellular cues that are necessary for the establishment of characteristic cell and fiber interactions in each brain region. During the development of the mammalian cerebral cortex, the early-generated cells line up in the most superficial part of the telencephalic pallium forming the preplate. It has been generally thought that the preplate derivatives are exclusively located in the cortical region and govern the early histogenetic phase of cortical development. However, we here disclose an unexpected evidence that a subset of early-generated neurons of the piriform preplate migrate inward into and disperse within the subcortical structure striatum during the embryonic stage. Their migratory route is unique and its direction is opposite to the ordinary migration of neuronal precursors directed outward from the periventricular germinal zone. After immigrating into the developing striatum, these early-generated cells are closely associated with the intrastriatal fascicules of axons. The majority of these cells are eliminated by apoptotic cell death during the early postnatal stage. Based on these findings, we propose a new concept: the preplate neurons may not only direct cortical histogenesis but also change their location to play a role in the development of subcortical structures.

Animals↗
PubMed2005

Effect of eggshell temperature during incubation on embryo development, hatchability, and posthatch development.

An experiment was conducted to study the effects of different eggshell temperature (EST) profiles during incubation on embryo mortality, hatchability, and embryo development. Furthermore, chicks from different EST profiles were reared under low and high housing temperatures to investigate subsequent posthatch growth and rectal temperature. Two batches of eggs were used in this experiment. Hatching eggs were subjected to 36.7 or 37.8 degrees C EST during the first week, to 37.8 degrees C EST during the second week, and to 37.8 or 38.9 degrees C EST during the third week of incubation. Posthatch housing temperature decreased from 35 degrees C at d 1 to 30 degrees C at d 7 (high) or decreased from 30 degrees C at d 1 to 25 degrees C at d 7 (low). The difference between machine temperature and EST (DT) was used to illustrate the effect of EST on heat production during incubation. DT differed per batch, and was smallest when eggs were incubated at 36.7 degrees C instead of 37.8 degrees C during wk 1. High EST during wk 3 of incubation (38.9 degrees C instead of 37.8 degrees C) reduced DT only in batch 2. Embryo development was most retarded in eggs incubated at 36.7 degrees C EST compared with at 37.8 degrees C during the first week of incubation. However, highest hatchability and embryo development were always found when EST was maintained at 37.8 degrees C constantly throughout incubation. Chicks that hatched from eggs incubated at low EST during wk 1 of incubation had lower rectal temperature after hatching, especially under low housing temperatures, and this effect lasted until 7 d posthatch in batch 1. The highest rectal temperatures were always found in chicks incubated at 37.8 degrees C EST constantly throughout incubation. Eggs and chicks from different batches require different environmental conditions for optimal embryo development, hatchability, and posthatch growth. Rearing temperature and incubation conditions affect the ability of young chicks to maintain their rectal temperature during the first week posthatch.

Animals↗
PubMed2000

Pubertal development and reproductive functions of Crl:CD BR Sprague-Dawley rats exposed to bisphenol A during prenatal and postnatal development.

Bisphenol A (BPA) is used on a large scale in the manufacture of polycarbonate plastics. BPA has been shown to bind weakly to both estrogen receptor (ER)alpha and ERbeta, and to transactivate reporter genes in vitro. The purpose of the present study was to determine whether exposure of rats to BPA during pre- and postnatal development affects estrogen-mediated end points related to pubertal development and reproductive functions. BPA was administered to pregnant Crl:CD BR Sprague-Dawley rats by gavage at 0, 3.2, 32, or 320 mg/kg/day from gestation day (GD) 11 through postnatal day (PND) 20. Diethylstilbestrol (DES) at 15 microg/kg/day was used as a reference chemical with known estrogenic effects. Female pubertal development was not affected by indirect BPA exposure of the offspring at any of the dose levels. Treatment with this chemical also did not produce detectable effects on the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA), estrous cyclicity, sexual behavior, or male reproductive organ weights of F(1) offspring. However, DES at 15 microg/kg/day increased the volume of the SDN-POA of female offspring and affected their normal estrous cyclicity following puberty. In this study, pre- and postnatal exposure of rats to BPA at 3.2, 32, or 320 mg/kg/day from GD 11 through PND 20 did not have any apparent adverse effects on female rat pubertal development and reproductive functions.

Animals↗
PubMed2001

Use of a stochastic model to develop understanding of the impact of different patterns of antiretroviral drug use on resistance development.

OBJECTIVE: To use a stochastic model to gain insights into the consequence for resistance development of different drug use patterns. METHODS: We consider use of three drugs (A, B and C) where for each drug one and only one viral mutation is associated with ability to replicate (effective reproductive ratio, R > 1) in the presence of that drug as monotherapy. For drug A mutation is a, etc. We define eight populations of short-lived infected cells that live 1 day: Vo with no mutations a, b, c; Va with mutation a only, Vab with mutations a and b, etc. A random number generator was used to determine whether mutations occur in any one round of replication and to sample from a Poisson distribution to determine for each cell the number of cells of the same population created in the next generation, using the R operative at that time. Values of R depended on drug exposure, cost of resistance and availability of target cells. RESULTS: Treatment strategies and the resulting percentage (over 100 runs) developing full "resistance" in 1500 days (Vabc not equal 0) were: (i) ABC 1500 days 0%; (ii) A 300 days, AB 300 days, ABC 900 days 100%; (iii) AB 300 days, ABC 1200 days 33%; (iv) ABC 2/3 1500 days 15%; (v) ABC 1/2 1500 days 100%; (vi) ABC 50 days, no drugs 50 days, for 1500 days 1%, where ABC 2/3 means on-drug for 2 days in every 3, ABC 1/2 represents on-drug for 1 day in every 2, and represents suboptimal adherence. CONCLUSIONS: This model helps to develop understanding of key principles concerning development of resistance under different patterns of treatment use.

Anti-HIV Agents↗
PubMed1999

HIV-associated immune dysfunction and delayed pubertal development in a cohort of young hemophiliacs. Hemophilia Growth and Development Study.

As part of the Hemophilia Growth and Development Study (HGDS), we investigated the relationship between HIV-associated immune dysfunction and delayed pubertal development in a cohort of 333 boys and adolescents with moderate or severe hemophilia who were between the ages of 6 and 19 years at study entry in 1989. Sixty-two percent of the cohort was infected with HIV in the late 1970s and early 1980s through exposure to contaminated clotting factor concentrates. The cohort was observed during follow-up at 6-month intervals; measurements taken at each follow-up visit included Tanner stage and CD4+ cell count. This analysis of data from the first 4 years of follow-up revealed statistically significant delays in pubertal development associated with increasing levels of immune dysfunction. Our results emphasize the importance of following pubertal development in HIV-infected adolescent boys since delays in maturation may reflect underlying disease progression.

Adolescent↗
PubMed1991

Expression of two members of the Wnt family during mouse development--restricted temporal and spatial patterns in the developing neural tube.

The Wnt gene family encodes a group of cysteine-rich proteins implicated in intercellular signaling during several stages of vertebrate development. This family includes Wnt-1 and Wnt-3, both discovered as activated oncogenes in mouse mammary tumors. Here we describe the molecular cloning of an additional member of the Wnt family, called Wnt-3A, and the spatial and temporal expression pattern of this gene as well as that of its close relative Wnt-3. The putative amino acid sequences of both proteins are almost 90% identical, but in situ hybridization to mouse embryo sections showed highly restricted patterns of expression of Wnt-3 and Wnt-3A, largely in separate areas in the developing nervous system. In the spinal cord Wnt-3 was expressed at low levels in the alar laminae and in the ventral horns, whereas Wnt-3A expression was confined to the roof plate. In the developing brain Wnt-3 was expressed broadly across the dorsal portion of the neural tube with a rostral boundary of expression at the diencephalon. In contrast, Wnt-3A was expressed in a narrow region very close to the midline; expression extended into the bifurcating telencephalon, in a highly localized fashion. Both Wnt-3 and Wnt-3A were expressed in the ectoderm, and Wnt-3A was also expressed in the periumbilical mesenchyme. Characteristic expression patterns of these two closely related genes suggest that Wnt-3 and Wnt-3A play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube.

Amino Acid Sequence↗
PubMed2005

Characterizing the grape transcriptome. Analysis of expressed sequence tags from multiple Vitis species and development of a compendium of gene expression during berry development.

We report the analysis and annotation of 146,075 expressed sequence tags from Vitis species. The majority of these sequences were derived from different cultivars of Vitis vinifera, comprising an estimated 25,746 unique contig and singleton sequences that survey transcription in various tissues and developmental stages and during biotic and abiotic stress. Putatively homologous proteins were identified for over 17,752 of the transcripts, with 1,962 transcripts further subdivided into one or more Gene Ontology categories. A simple structured vocabulary, with modules for plant genotype, plant development, and stress, was developed to describe the relationship between individual expressed sequence tags and cDNA libraries; the resulting vocabulary provides query terms to facilitate data mining within the context of a relational database. As a measure of the extent to which characterized metabolic pathways were encompassed by the data set, we searched for homologs of the enzymes leading from glycolysis, through the oxidative/nonoxidative pentose phosphate pathway, and into the general phenylpropanoid pathway. Homologs were identified for 65 of these 77 enzymes, with 86% of enzymatic steps represented by paralogous genes. Differentially expressed transcripts were identified by means of a stringent believability index cutoff of > or =98.4%. Correlation analysis and two-dimensional hierarchical clustering grouped these transcripts according to similarity of expression. In the broadest analysis, 665 differentially expressed transcripts were identified across 29 cDNA libraries, representing a range of developmental and stress conditions. The groupings revealed expected associations between plant developmental stages and tissue types, with the notable exception of abiotic stress treatments. A more focused analysis of flower and berry development identified 87 differentially expressed transcripts and provides the basis for a compendium that relates gene expression and annotation to previously characterized aspects of berry development and physiology. Comparison with published results for select genes, as well as correlation analysis between independent data sets, suggests that the inferred in silico patterns of expression are likely to be an accurate representation of transcript abundance for the conditions surveyed. Thus, the combined data set reveals the in silico expression patterns for hundreds of genes in V. vinifera, the majority of which have not been previously studied within this species.

DNA, Complementary↗
PubMed2002

Life course health development: an integrated framework for developing health, policy, and research.

The life course health development (LCHD) framework organizes research from several fields into a conceptual approach explaining how individual and population health develops and how developmental trajectories are determined by interactions between biological and environmental factors during the lifetime. This approach thus provides a construct for interpreting how people's experiences in the early years of life influence later health conditions and functional status. By focusing on the relationship between experiences and the biology of development, the LCHD framework offers a better understanding of how diseases occur. By suggesting new strategies for health measurement, service delivery, and research, as well as for improving health outcomes, this framework also supports health care-purchasing strategies to develop health throughout life and to build human health capital.

Guidelines as Topic↗
PubMed1998

Regulation of GM-CSF-induced dendritic cell development by TGF-beta1 and co-developing macrophages.

Using a culture system of bone marrow progenitor cells with GM-CSF and TGF-beta1, a study was performed to analyze the effect of TGF-beta1 on the development of dendritic cells (DC) and to elucidate the regulatory role of macrophages co-developing with dendritic cells. The results demonstrate that DC generated in the presence of TGF-beta1 were immature with respect to the expression of CD86, nonspecific esterase activity and cell shape. Such inhibitory effects of TGF-beta1 were dependent on FcR+ macrophages, which were depleted by panning. TGF-beta1 did not appear to inhibit the commitment of progenitor cells to the DC lineage. In addition, TGF-beta1 also acted directly on the intermediate stage of DC to prevent their over-maturation, which results in a preferential decrease in MHC class II, but not in CD86, in the presence of TNF-alpha. FcR+ suppressive macrophages were also shown to facilitate DC maturation when stimulated via FcR-mediated signals even in the presence of TGF-beta1. These results indicate that TGF-beta1 indirectly and directly regulate the development of DC and that co-developing macrophages have a regulatory role in DC maturation.

Animals↗
PubMed1996

A presentation of a conceptual framework and its use in the definition of nursing development within a number of nursing development units.

This paper provides a conceptual framework upon which action plans can be built to enable registered nurses to reflect upon their work and practice activities. This conceptual framework has been used by the author in his work with various nursing development units within Yorkshire, England, in his role as their academic nurse advisor. The framework has been useful in helping nurses not only to reflect upon current work and practice activities but also as a guideline for future development. The paper provides examples of such nursing development activities and includes a personal view of how nursing development units can act as catalysts for change.

Clinical Nursing Research↗