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E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas.

The E2A gene products, E12 and E47, are critical for proper early B-cell development and commitment to the B-cell lineage. Here we reveal a new role for E2A in T-lymphocyte development. Loss of E2A activity results in a partial block at the earliest stage of T-lineage development. This early T-cell phenotype precedes the development of a T-cell lymphoma which occurs between 3 and 9 months of age. The thymomas are monoclonal and highly malignant and display a cell surface phenotype similar to that of immature thymocytes. In addition, the thymomas generally express high levels of c-myc. As assayed by comparative genomic hybridization, each of the tumor populations analyzed showed a nonrandom gain of chromosome 15, which contains the c-myc gene. Taken together, the data suggest that the E2A gene products play a role early in thymocyte development that is similar to their function in B-lineage determination. Furthermore, the lack of E2A results in development of T-cell malignancies, and we propose that E2A inactivation is a common feature of a wide variety of human T-cell proliferative disorders, including those involving the E2A heterodimeric partners tal-1 and lyl-1.

Animals↗

Involvement of consumers in the development of evidence based clinical guidelines: practical experiences from the North of England evidence based guideline development programme.

BACKGROUND: Consumer involvement in clinical guidelines has long been advocated although there are few empirical accounts of attempts to do so. It is therefore not surprising that there is a lack of clarity about how and when to involve consumers and what to expect from them within the process of guideline development. METHODS: The North of England evidence based guideline development programme has used four different methods of consumer involvement. RESULTS: When individual patients were included in a guideline development group they contributed infrequently and had problems with the use of technical language. Although they contributed most in discussions of patient education, their contributions were not subsequently acted on. In a "one off" meeting with a group of patients there were again reported problems with medical terminology and the group were most interested in sections on patient education and self management. However, their understanding of the use of scientific evidence in order to contribute to a more cost effective health care remained unclear. In a workshop it was possible to explain the technical elements of guideline development to patients who could then engage with such a process and make relevant suggestions as a consequence. However, this was relatively resource intensive. A patient advocate within a guideline development group felt confidence to speak, was used to having discussions with health professionals, and was familiar with the medical terminology. CONCLUSIONS: Consumers should be involved in all stages of guideline development. While this is possible, it is not straightforward. There is no one right way to accomplish this and there is a clear need for further work on how best to achieve it.

Decision Making, Organizational↗

Developing mouse Sertoli cells in vitro: effects on developing ovaries in co-culture and production of anti-Müllerian hormone.

Previous work in our laboratory showed that pre-Sertoli cells adopt an epithelial phenotype when cultured in the presence of reconstituted basement membrane (RBM), and so cultures were established with and without this substrate. Biological activity of isolated developing mouse Sertoli cells maintained in vitro was assessed in the current study by utilising a co-culture approach, to determine whether the cells were capable of affecting ovarian differentiation. Developing Sertoli cells isolated at embryonic day (E) 12.5 exerted a deleterious effect on E12.5 ovaries in co-culture, inducing a loss of germ cells. However, when cells were isolated a day later and co-cultured with E13.5 ovaries (after entry to meiosis has begun), germ cells survived and showed evidence of meiosis, although ovigerous cords in co-cultures were masculinized compared to those of control cultured ovaries. Thus, both stages examined showed biological effects; cultured pre-Sertoli cells explanted at E12.5 showed a negative effect on female germ cells, whereas those explanted at E13.5 masculinized ovigerous cords. The functional status of isolated developing mouse Sertoli cells in vitro was further assessed by immunocytochemistry to investigate the expression of anti-Müllerian hormone, an early product of pre-Sertoli cells. Positive immunostaining was seen in developing Sertoli cells in vitro, particularly where cells had been explanted to an RBM substrate, demonstrating that good epithelial morphology is associated with improved function. Our culture system is therefore well suited for investigating factors produced by developing Sertoli cells, their role in influencing testicular morphogenesis and their potential to perturb ovarian differentiation. We believe that this in vitro approach provides a more physiological assessment compared with the knockout mouse model, where global effects of genes with housekeeping functions can compromise overall development.

Animals↗

The Eating Disorders Section of the Development and Well-Being Assessment (DAWBA): development and validation.

OBJECTIVE: Development and validation of the Eating Disorders Section of the Development and Well-Being Assessment (DAWBA). It is a package of questionnaires, interviews and evaluation techniques, designed to generate DSM-IV and ICD-10 based diagnoses of anorexia, bulimia nervosa and the respective partial syndromes in epidemiological studies, in subjects who are 7 to 17 years old. The parents are interviewed in all cases, as are young people aged 11 or more. METHODS: 174 girls, divided into three groups, were assessed with the Eating Disorders Section of the Development and Well-Being Assessment: 48 with eating disorders, 55 clinical controls (with depression, obsessive-compulsive disorder or gastrointestinal disease) and 71 community controls. The sensitivity, specificity and predictive values of the assessment were investigated by comparing the Development and Well-Being Assessment diagnoses with independent psychiatric diagnoses. The test-retest reliability was investigated by reapplying the measure on 55 subjects after 2 or 3 weeks. RESULTS: For the detection of any DSM-IV and ICD-10 eating disorder, the final Development and Well-Being Assessment diagnosis had a sensitivity of 100%, specificity of 94%, positive predictive value of 88%, and a negative predictive value of 100%; there was 95% agreement between the initial and repeat diagnoses (a kappa of 0.81). CONCLUSION: The Eating Disorders Section of the Development and Well-Being Assessment has suitable psychometric properties for use in clinical and epidemiological studies.

Adolescent↗

How the developing septo-preoptic medical basal hypothalamus stimulates the development of placode-derived LHRH neurons.

We examined the effects of the developing cerebral cortex (CC) and septo-preoptic medial basal hypothalamus (S-MBH) on the development of LHRH neurons in vitro. The serum-free basal culture medium (BCM) was supplemented with CC or S-MBH extracts prepared from 18.5-day-old embryos or from 2-day-old newborns, and the olfactory placode (NAP) of 12-day-old embryos was cultured. The migration of LHRH neurons was found on Day 3 in the cultures supplemented with the embryonic S-MBH extract (Group 3), where the cell development proceeded showing a numerical increase of the cells and the elongation of neurites. In cultures supplemented with the newborn S-MBH extract (Group 5), the cell development was less intensive in comparison with that of Group 3, while in cultures which had no brain extracts (Group 1), the neurons failed to survive a long term culture. The effects of the CC were less than of S-MBH extracts. Analysis of the protein composition of the extracts by electrophoretic and immunoblotting examinations demonstrated a protein spot of 70-kD in the embryonic S-MBH extract. Because the protein spot was identified to be alpha-fetoprotein (AFP), we further examined the effects of AFP. When the anti-AFP immunoglobulin was added to the Group 3 culture, the stimulative effects of the embryonal extract were inhibited, and the addition of AFP to Group 1 cultures did not show stimulative effects. We conclude that the developing S-MBH, the migrating target of LHRH neurons, contains some essential factors for the development of LHRH neurons, but further analysis is needed to determine the chemical natures of these factors.

Animals↗

The effects of experimental unilateral anotia on skull development in the chick embryo. III. Chondrocranial development in anotic embryos of 7-20 days of incubation.

The study of the development of of the chondrocranium in chick embryos with unilateral (right-sided) anotia revealed the following main characteristics. 1. The median axes of the chordal and the prechordal part of the cranial base are not in a straight line but show a deviation toward the right side. The angle between the two axes has its vertex in the region of the foramen hypophyseos. 2. The metotic cartilage and the foramina of the IXth and Xth cranial nerves are normal in position. 3. The tectum synoticum develops later and to a lesser extent than normal. 4. Between the basal plate, the metotic cartilage, the occipital arch and the supracapsular cartilage a foramen is formed which, later in development, is closed by outgrowths of the metotic cartilage and the basal plate. 5. The "optic area" shows a practically normal appearance which indicates that the cartilaginous ventral wall of the lagenal capsule is of basal plate origin. 6. The pro-otic process develops practically normal and, hence, is independent of the ear capsule. 7. The quadrate cartilage and the right lower jaw are displaced ventro-posteriorward. The earliest development of the perichondral bones shows some particularities which are closely correlated with the development of the various cartilaginous structures.

Animals↗

[A physiological development time-based simulation model for cotton development stages and square- and boll formation].

In this study, three cotton varieties (CRI 36, CRI 35 and CRI 41) were planted in Nanjing, Anyang, Baoding and Shihezi, respectively, in 2002, and the dynamic relationships between their development and environmental factors were analyzed. Based on this, a simulation model for cotton development stages and square-and boll development was built in terms of physiological development time (PDT). In calculating relative thermal effectiveness, the effect of diurnal temperature differences in different regions on cotton development was incorporated, and the enhancement of plastic mulching on air temperature was quantified. To simulate development stages, the initial fruiting node index (IFIN), sunlight duration factor (FSH), and solar radiation index on fruiting branch (IFBR) were introduced, besides earliness factor of a given genotype. The validation of the model with the data obtained from different years, ecological zones, genotypes, and cultivation practices indicated a high goodness of fitness between the simulated results and observed values. The root mean square error (RMSE) between simulated and observed days from sowing to emergence, emergence to squaring, anthesis to boll opening, and sowing to boll opening was 0.9, 2.2, 1.7, and 2.1 d, respectively, with a mean of 2.1 d, and in all plant sites, the RMSE between simulated and observed days from squaring to boll opening was 1.8-3.7 d, and that from squaring to opening was 4.6-5.8 d.

Gossypium↗

[The early development of Jacobson's organ in the nasal cavity of the rat before the inception of the secondary palatal development].

The early development of Jacobson's organ was studied by means of a series of embryos of the rat which were of various ages and exactly dated. Already at the youngest stage of those rats, the nasal cavity is just an open groove, the organ is a thickened epithelial layer at the medial nasal process. Only 15 h later, while the nasal grooves start to close from caudal to rostral, Jacobson's organ has acquired the shape of a deep, long cleft, situated within the broad nasal opening. On the 13th d of fetal life, a complete, caudally closed nasal cavity appears. By the means of fundamental growth changes, the already well developed organ has become shifted to a more caudal position and lies now above the primary palate. A shorter caudal part of the still cleft-like organ just starts to close itself thus forming its typical tube-like structure. Moreover strong nerve bundles running from Jacobson's organ to the brain indicate that in the meantime a sensory epithelium can be distinguished. Up to the 15th d of development, the tube-forming process of Jacobson's organ is completed. Parallel to this procedure, the surrounding nasal cavity acquires a caudal apertura nasalis interna by the rupture of the membrana bucconasalis while Jacobson's organ still lies above the rostral primary palate. Primary in the medial, somewhat later in the lateral part of the nasal cavity, first outlines of cartilage appear, visible as dense cell formations. Together with this, the paraseptal cartilage, in these stages closely connected to the septal cartilage, develops quite early. Between the 14th and 15th d of its fetal life, the flat, tube-formed Jacobson's organ of the rat gets turned from a primary horizontal into a vertical position, which brings its sensory epithelium to the medial side. It is assumed that this happens for functional reasons. Because of the obviously early and progressive development of Jacobson's organ within that of the nasal cavity, it seems to be probable that already the origin of the nose, the olfactory placodes, are determined in the directions both of the nasal cavity and of Jacobson's organ. Furthermore the results demonstrate an early preferential development of Jacobson's organ in comparison to that of the surrounding nasal cavity.

Animals↗

Influence of repeated exposure to rapidly developing hypoxaemia on the arousal and cardiopulmonary response to rapidly developing hypoxaemia in lambs.

Experiments were done on four lambs to determine if repeated exposure to rapidly developing hypoxaemia influences the cardiopulmonary and arousal response from sleep. Each lamb was anaesthetized and instrumented for sleep staging and measurements of arterial haemoglobin oxygen saturation. No sooner than three days after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing 21% oxygen and during experimental periods of rapidly developing hypoxaemia when the animal was breathing 5% oxygen for approximately 100 epochs of sleep. Arousal occurred from both sleep states during rapidly developing hypoxaemia but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial haemoglobin oxygen saturation were significantly increased with repeated exposure to rapidly developing hypoxaemia during both quiet sleep and active sleep. Thus, our data provide evidence that repeated exposure to rapidly developing hypoxaemia produces an arousal response decrement in lambs. Since it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanism of the arousal response decrement following repeated exposure to rapidly developing hypoxaemia are warranted.

Animals↗

Fetal development of striated and smooth muscle sphincters of the male urethra from a common primordium and modifications due to the development of the prostate: an anatomic and histologic study.

BACKGROUND: The aim of the study was to investigate the development of the human urethral sphincter complex during fetal development. METHODS: 23 human male fetal specimens were investigated. The histological sections were processed according to the epoxy resin-based plastination technology. RESULTS: At 9th week of gestation, a combined sphincteric primordium of the rhabdosphincter and the lissosphincter is situated at the anterior and lateral aspects of the membranous and prostatic urethra. Both muscular components assume an omega-shaped configuration due to the presence of a constant connective tissue raphe posterior to the urethra that anchors the rhabdosphincter in the perineal body. Development of the prostate laterally and posteriorly does not modify the growth of the urethral sphincter complex anteriorly but inhibits its development laterally and posteriorly. CONCLUSIONS: The important morphological characteristics of the male adult rhabdosphincter and lissosphincter can be seen very early in fetal development.

Fetal Development↗

The development of voltage-gated ion channels and its relation to activity-dependent development events.

Spontaneous activity is an essential feature in the development of the nervous system. The patterns of activity and the waveform and ionic dependence of the action potentials that occur during such activity are fine-tuned to carry out certain developmental functions, and are therefore generally not compatible with the mature physiological function of the cell. For this reason, the patterns of ion channel development that create spontaneous activity early in the development of a given cell type are complex and not easily predicted from the mature properties of that same cell. Ion channels are often found that are specific to early stages of development, and that either are not retained in the mature cell or whose properties are greatly changed during later differentiation. The exact significance of such patterns of channel development is just now becoming clear, as we understand more about the mechanisms linking spontaneous activity to later developmental events.

Animals↗

Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries.

BACKGROUND: Obesity is increasing worldwide because developing countries are adopting Western high-fat foods and sedentary lifestyles. In parallel, in many of them, hypertension is rising more rapidly, particularly with age, than in Western countries. OBJECTIVE: To assess the relationship between adiposity and blood pressure (BP) in a developing country with high average BP (The Seychelles, Indian Ocean, population mainly of African origin) in comparison to a developed country with low average BP (Switzerland, population mainly of Caucasian origin). DESIGN: Cross-sectional health examination surveys based on population random samples. SETTING: The main Seychelles island (Mahé) and two Swiss regions (Vaud-Fribourg and Ticino). SUBJECTS: Three thousand one hundred and sixteen adults (age range 35-64) untreated for hypertension. MEASUREMENTS: Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), systolic and diastolic blood pressure (SBP and DBP, mean of two measures). METHODS: Scatterplot smoothing techniques and gender-specific linear regression models. RESULTS: On average, SBP and DBP were found to increase linearly over the whole variation range of BMI, WHR and WC. A modest, but statistically significant linear association was found between each indicator of adiposity and BP levels in separate regression models controlling for age. The regression coefficients were not significantly different between the Seychelles and the two Swiss regions, but were generally higher in women than in men. For the latter, a gain of 1.7 kg/m(2) in BMI, of 4.5 cm in WC or of 3.4% in WHR corresponded to an elevation of 1 mmHg in SBP. For women, corresponding figures were 1.25 kg/m(2), 2.5 cm and 1.8% respectively. Regression coefficients for age reflected a higher effect of this variable on both SBP and DBP in the Seychelles than in Switzerland. CONCLUSION: These findings suggest a stable linear relation of adiposity with BP, independent of age and body fat distribution, across developed and developing countries. The more rapid increase of BP with age observed in the latter countries are likely to reflect higher genetic susceptibility and/or higher cumulative exposure to another risk factor than adiposity.

Abdomen↗

Assessing children's development using parents' reports. The Child Development Inventory.

The Child Development Inventory (CDI), completed by parents at home, assesses the development of social, self-help, motor, language, letter and number skills, and presence of symptoms and behavior problems of children between the ages of 15 months and 5 years. The results provide the pediatrician with a profile of the child's development, problems, and strengths, and are an aid to comprehensive assessment. CDI norms and validity were determined for a community sample of 568 children. The CDI developmental scales correlate closely with age (r = 0.84). CDI results identified all the normative group children who were enrolled in early childhood/special education (N = 26) and correlated with academic achievement for children in kindergarten (N = 132). CDI scales correlated with reading achievement in kindergarten as follows: general development 0.69, letters 0.56, language comprehensive 0.42, expressive language 0.36, and self-help 0.35. Thus, the CDI provides a useful measure of children's development and, because of its reliance on parental reports, offers an effective approach to developmental assessment in the busy pediatric practice.

Case-Control Studies↗

Comparing gay identity development theory to cognitive development: an empirical study.

The relationship between gay identity development and cognitive development, as outlined by Ivey's Developmental Counseling Therapy Model, was explored. The Gay Identity Questionnaire and the Standard Developmental Counseling Interview were administered to 78 gay men. Results suggested that there is a relationship between gay identity development and cognitive development. In addition, the findings provide evidence that gay identity development can be categorized by concrete and abstract frames of reference.

Adult↗

Physical assessment: a vital nursing tool in both developing and developed countries.

In developed countries such as the United States and Great Britain, the use of technology to assess and diagnose a patient's health status is often taken for granted. In developing countries, however, the lack of available technology, replacement parts, and ability to maintain the machinery is severely limited. More often than not, diagnosis and consequent treatment are decided through physical assessment findings alone. It is therefore imperative that critical care nurses in developing countries acquire and utilize good physical assessment skills to enhance quality nursing care. This article focuses on physical assessment skills from a global perspective, emphasizing the value of this knowledge and its application to clinical practice for critical care nurses in both developing and developed countries.

Critical Care↗

[Medical development cooperation in the Confederation. The international framework and the important place of public health in Swiss development cooperation].

The systematic organization of health services in the developing countries to benefit the majority of the population is seen as an important contribution toward the general economic and social development of these countries. This view is uncontested today, but was given less importance in the early years of Swiss development aid. The Swiss Development Cooperation's support of health services is now integrated into its overall program to satisfy the basic needs of the people of the developing countries.

Developing Countries↗

Development of bladder and bowel control: significance of prematurity, perinatal risk factors, psychomotor development and gender.

UNLABELLED: Development of bladder and bowel control from 6 months to 6 years was investigated in 140 preterm children and a control group of 349 healthy term children. Structured parental interviews and neurodevelopmental assessments were carried out when the child was 1, 3, 6, 9, 12, 18 and 24 months, and at yearly intervals thereafter. Even though preterm children were put on the potty at significantly earlier ages and significantly more frequently than term children, they expressed their need for evacuation and attained day and night bladder and bowel control at the same corrected age as term children. Initiation and intensity of toilet-training were not significantly correlated with the development of bladder and bowel control. Gestational age, being too small for gestational age, adverse perinatal conditions and mild to moderate neurological impairment did not affect the occurrence of the child's initiative and the development of bladder and bowel control. Neither developmental and intelligence quotients at the age of 1 to 3 years nor the socioeconomic status of the families influenced the age at which the child became clean and dry. Girls were significantly more advanced in expressing their needs and gaining bladder and bowel control than boys in both the preterm and term groups. CONCLUSION: Development of bladder and bowel control is largely a maturational process which cannot be accelerated by an early onset or a high intensity of training. It is not affected by prematurity, adverse perinatal events or mild to moderate neurological impairment, nor is it related to psychomotor development or actual Swiss socioeconomic conditions.

Child Development↗

Development of striatal dopaminergic function. I. Pre- and postnatal development of mRNAs and binding sites for striatal D1 (D1a) and D2 (D2a) receptors.

Quantitative receptor autoradiography with iodinated ligands, quantitative in situ hybridization histochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to describe the prenatal and early postnatal ontogeny (embryonic day 14 to postnatal day 7, or E14 to P7) of striatal D1 and D2 dopamine receptor binding sites and mRNA levels, respectively, in relation to the development of dopaminergic nigrostriatal innervation D1 dopamine receptor, measured by [125I]SCH23982 binding, and dopamine transporter binding sites, measured by [125I]RTI-55 binding, were present in low amounts beginning on E14 (2-3% and 0.3-0.6% of adult values, respectively) and increased slowly during the prenatal period. D2 receptor binding sites, measured with [125I]spiperone, were also detected on E14 but in higher relative quantities (17% of adult values) than D1 receptor and dopamine transporter binding sites at the same age. Other than abrupt declines in the late prenatal period for D1 and D2 receptor binding sites, all three binding sites increased throughout development and increased maximally between P7 and adulthood. On P5, both D1 and D2 receptors were functionally coupled to their respective G proteins, based on GTP-induced decreases in affinity of dopamine for [125I]SCH23982 and [125I]spiperone binding. D1 receptor mRNA was present in E14 striatal anlage, increased prenatally, declined on P0, then increased to a peak on P5, after which it declined to its lowest levels (20% of peak values) in the adult. In contrast, D2 receptor mRNA levels were presented also on E14, increased to a peak on P0, declined until P5, and increased thereafter to adulthood. Anatomically, nigrostriatal innervation and D1 and D2 receptor mRNA levels increased from the medial to lateral striatal quadrants. In contrast, D1 and D2 receptor binding site ontogency exhibited fairly homogenous distributions from E18 to P7. D1 and D2 receptor mRNAs appear to be expressed early in prenatal development before there is any significant dopaminergic innervation. In contrast, the majority of D1 and D2 receptor binding activity, representing expressed receptor proteins, develops in the postnatal period and correlates well with the increase in dopaminergic innervation. Intrinsic genetic programming is more likely to be responsible for D1 and D2 receptor gene transcription in striatal neuroblasts and newly born neurons, while factors derived from ingrowing dopaminergic afferents may direct post-transcriptional dopamine receptor development. The dissociation between the ontogeny of dopamine receptor binding sites and mRNAs suggests that the developmental regulation of D1 and D2 receptor synthesis is independent of D1 and D2 receptor gene transcription.

Animals↗