SEARCH · PubMed Health

Results for “Developability”

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

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

At least 703 records · Page 39Linked to original sources

PubMed2005

Further psychometric property development of the Menopause-Specific Quality of Life questionnaire and development of a modified version, MENQOL-Intervention questionnaire.

OBJECTIVES: To develop the 1996 MENQOL questionnaire further with advice regarding summary score computation, missing-data management, readability, recall period and assessment of the vasomotor domain reliability and construct validity. To develop a modified version, the MENQOL-Intervention questionnaire, for use where certain treatment side effects could negatively impact the quality of life. METHODS: MENQOL-Intervention modifications involved the addition of three items to the physical domain. For both questionnaires, psychometric property assessment was embedded in two randomized controlled trials of menopause interventions. Test-retest reliability and Cronbach's alpha were computed for all domains as was construct validity of the vasomotor domain for both questionnaires. RESULTS: The vasomotor intraclass correlation coefficient was 0.73 for the MENQOL-Intervention over 1 week and 0.78 for the MENQOL over 1 month. The altered physical domain of the MENQOL-Intervention questionnaire continued to show strong test-retest reliability and Cronbach's alpha consistent with the MENQOL. The MENQOL-Intervention demonstrated excellent face validity with high construct validity for the vasomotor domain of 0.78-0.80. For both instruments, comparisons of the vasomotor domains to hot flash scores, although statistically significant, were only moderate at 0.56 and 0.49. CONCLUSIONS: Both the MENQOL and the MENQOL-Intervention questionnaires show strong psychometric properties. We recommend using the MENQOL-Intervention questionnaire where intervention side effects might negatively impact a woman's quality of life. For both questionnaires, a summary score can be calculated.

Breast↗

PubMed2006

Inborn errors of development: disruption of pathways critical for normal development.

Traditionally, congenital birth defects have been classified descriptively based on the observed defects. As the genes important for some birth defects have been identified, it is clear that several of the genes mutated in malformation syndromes or genes whose expression is disrupted by environmental agents or teratogens are part of conserved signal transduction pathways. One can consider malformations to be inborn errors of development whereby pathways important for controlling development throughout evolution have been disrupted. This article focuses on three highly conserved pathways and their interactions and provides a framework that allows pediatricians to relate the phenotype of humans who have developmental disorders to the functions of genes in a signal transduction pathway.

Body Patterning↗

PubMed2006

From discovery to development: current industry perspectives for the development of novel methods of helminth control in livestock.

Despite the extraordinary success in the development of anthelmintics in the latter part of the last century, helminth parasites of domestic ruminants continue to pose the greatest infectious disease problem in grazing livestock systems worldwide. Newly emerged threats to continuing successful livestock production, particularly with small ruminants, are the failure of this chemotherapeutic arsenal due to the widespread development of anthelmintic resistance at a time when the likelihood of new products becoming commercially available seems more remote. Changing public attitudes with regards to animal welfare, food preferences and safety will also significantly impact on the ways in which livestock are managed and their parasites are controlled. Superimposed on this are changes in livestock demographics internationally, in response to evolving trade policies and demands for livestock products. In addition, is the apparently ever-diminishing numbers of veterinary parasitology researchers in both the public and private sectors. Industries, whether being the livestock industries, the public research industries, or the pharmaceutical industries that provide animal health products, must adapt to these changes. In the context of helminth control in ruminant livestock, the mind-set of 'suppression' needs to be replaced by 'management' of parasites to maintain long-term profitable livestock production. Existing effective chemical groups need to be carefully husbanded and non-chemotherapeutic methods of parasite control need to be further researched and adopted, if and when, they become commercially available. This will require veterinary parasitology researchers from both the public and private sectors to work in close co-operation to ensure 'sustainability' - not only of the livestock industries that they service - but also for their very own activities and enterprises.

Animal Welfare↗

PubMedDate not supplied

Toward the rational development of peptidomimetic analogs of the C-terminal endothelin hexapeptide: development of a theoretical model.

In an early report on the structure-activity relationship of endothelin (ET) peptides, it was reported that the C-terminal hexapeptide ET(16-21), His-Leu-Asp-Ile-Ile-Trp, is the minimum ET fragment which maintains biological activity in some, but not all the tissues responding to ETs. Subsequently, other authors described a series of analogs of this peptide, in which the His 16 residue was replaced by non-natural amino acids, characterized by bulky aromatic side chains. Among them, two well-characterized non-selective ETA/ETB antagonists were PD 142893 and PD 145065; interest in these potent ET antagonists was, however, reduced by their peptidic structure which was likely to lead to undesirable properties such as poor bioavailability and short duration of action. On the basis of these premises, our previous studies led to the development of a peptidomimetic ligand of ET receptors (compound 3), based on the replacement of the His 16 residue of ET(16-21) with an (E)-N-(benzyloxy)iminoacyl moiety; compound 3 proved to possess a certain affinity for ET receptors, albeit lower than that shown by PD 142893 and PD 145065. We report here on ETA/ETB binding affinity of compounds 4-12, designed as a new series of ET(16-21) analogs. Compounds 4 and 5 were practically devoid of any affinity; derivatives 6-12 exhibited appreciable affinity indices for ETB receptors higher than that shown by 3, even if still lower than that obtained for PD 145065. This paper also describes the development of a pharmacophoric model able to explain the ET receptor binding properties of our hexapeptide analogs compared with those of PD 142893 and PD 145065 and IRL2500, recently reported as a potent ETB selective endothelin antagonist.

Amino Acid Sequence↗

PubMed1998

The rates of adhesion development and the effects of crystalloid solutions on adhesion development in pelvic surgery.

OBJECTIVE: To document rates of adhesion development after abdomino-pelvic surgery, stratified by adhesion type, access method, and use of crystalloid solution instillates. DESIGN: Reports from a MEDLINE search (1/1/1966-12/18/1996) detailing rates of adhesion development and meeting the inclusion criteria were subjected to meta-analysis. SETTING: Meta-analysis. PATIENT(S): Patients undergoing abdomino-pelvic surgery. INTERVENTION(S): Intraperitoneal crystalloid solution instillates. MAIN OUTCOME MEASURE(S): Percentage adhesion-free outcome in patients ("patients") or surgical sites ("sites"). RESULT(S): Adhesion-free outcome (sites) was lowest for reformed (26.3% laparotomy; 14.3% laparoscopy), higher for de novo 1b (direct trauma) (45.2% laparotomy, 37.2% laparoscopy), and highest for de novo 1a (indirect trauma) adhesions (82.4% laparoscopy). Crystalloid solution instillates reduced adhesion-free outcome at sites (45.2% versus 20% de novo 1b adhesions in laparotomy) and in patients (43.5% versus 19.9% reformed, laparotomy; 71.7% versus 25% de novo 1b, laparoscopy). CONCLUSION(S): Adhesion-free outcome was lowest for reformed, higher for de novo 1b, and highest for de novo 1a adhesions. Surprisingly, it was lower in laparoscopy than in laparotomy for de novo 1b and reformed adhesions. Crystalloid instillates did not increase adhesion-free outcome. Although limited by the retrospective and heterogeneous nature of the data, these conclusions nonetheless provide a basis on which to formulate future hypotheses.

Crystallization↗

PubMed1998

Development of monoclonal antibodies specific for human glandular kallikrein (hK2): development of a dual antibody immunoassay for hK2 with negligible prostate-specific antigen cross-reactivity.

OBJECTIVES: Human glandular kallikrein (hK2) is a protein that is 80% homologous to prostate-specific antigen (PSA), and, like PSA, is localized to the prostate. We developed a specific immunoassay for hK2 that can be used to evaluate its clinical diagnostic utility. METHODS: We developed monoclonal antibodies (mAbs) specific for hK2 by immunizing with hK2 and screening for clones reactive with hK2 and not PSA. Prototype sandwich assays using these mAbs were tested, and the optimum pair selected. Purified hK2 was used as standard and PSA cross-reactivity was assessed in the assay. Both hK2 and hK2-alpha1-antichymotrypsin (ACT) complexes have been identified in sera of patients with prostate cancer (PCa). Serum samples (n = 671) from healthy volunteers and patients with prostate disease were assayed for hK2 and PSA levels. RESULTS: The assay had a detection limit of less than 0.12 ng/mL and a less than 0.5% cross-reactivity with PSA. The assay preferentially detected free hK2 with a 3.5-fold higher molar response than with hK2-ACT. The mean serum concentration of hK2 in normal control samples was low (0.33 and 0.37 ng/mL for normal healthy men and women, respectively) but was elevated in patients with prostate disease (0.86 and 6.77 ng/mL for patients with benign prostatic hyperplasia and PCa, respectively). Negligible cross-reactivity to hK2 was measured by Tandem PSA assays (Hybritech). CONCLUSIONS: Significant concentrations of hK2, relative to PSA, were detected in human serum, especially in patients with prostate disease. Serum hK2 concentrations were not proportional to PSA concentration. Therefore, hK2 has the potential to be an independent and clinically useful marker for PCa.

Antibodies, Monoclonal↗

PubMed1999

Growing up on the streets: why B-cell development differs from T-cell development.

B-cell development differs significantly from T-cell development in that negative selection of autoreactive B cells can occur in the same microenvironment in which productive immune responses begin. Here, Sarah Townsend and colleagues discuss how this 'growing up on the streets' might provide a mechanism that fills holes in the B-cell repertoire, much as major histocompatibility complex polymorphism fills holes in the T-cell repertoire.

Animals↗

PubMed1987

Childhood hepatocellular carcinoma develops exclusively in hepatitis B surface antigen carriers in three decades in Taiwan. Report of 51 cases strongly associated with rapid development of liver cirrhosis.

To elucidate the etiologic role of chronic hepatitis B virus (HBV) infection and the role of liver cirrhosis in hepatocellular carcinoma (HCC), pathologic and virologic features of the disease were studied in 51 children with HCC; these accounted for 4.3% of 1195 pathologically proven HCC patients examined in the last three decades. Males predominated (M/F = 3.3:1), and the mean age was 11 years (range: 4-15 years). Hepatitis B surface antigen (HBsAg) was detected in the liver and/or serum of 100% of 42 children by immunocytochemical and/or radioimmunoassay, in the serum of 90% of 10 siblings, and more importantly in 94.1% of 17 mothers, suggesting that infection from familial HBsAg carriers, particularly carrier mothers, may contribute to the high incidence. Liver cirrhosis was frequent (74%), especially in the unresectable cases (87%); in the 20 children under 9 years of age, 95% were cirrhotic, a significantly higher level than the 58% of the 26 older children, P less than 0.005. All but one had advanced HCC, with 1-year survival in only 10.5%. The advanced HCC coupled with young age suggests that HCC can develop rapidly. The low positive rates of serum hepatitis B e antigen (HBeAg, 18%) and liver hepatitis B core antigen (11%) coupled with high frequency of liver cirrhosis indicate that an early HBeAg seroconversion to anti-HBe, in association with severe liver injury, may play an important role in the rapid development of HCC in children.

Adolescent↗

PubMed2002

Ocular development-associated gene (ODAG), a novel gene highly expressed in ocular development.

Complementary DNA (cDNA) arrays were used to detect highly expressed messenger RNA (mRNA) at postnatal day 2 (P2) and P10 in the mouse eye, and several clones highly expressed at P2 were isolated. We focused among them on a novel gene, the ocular development-associated gene (ODAG), which was down regulated at P10. The expression around birth was subsequently confirmed by reverse transcription-polymerase chain reaction. Mouse ODAG cDNA encodes a protein of 266 amino acids. Human ODAG cDNA and genomic structure were identified by basic local alignment search tool analysis of the GenBank database with mouse ODAG. Mouse ODAG-specific mRNA expression was detected in various mouse tissues within the eye at P2 and P7, whereas it was not detected anywhere at P14, suggesting that ODAG may play a role in eye development.

Amino Acid Sequence↗

PubMed1997

Apoptosis in development and disease of the nervous system: 1. Naturally occurring cell death in the developing nervous system.

In recent years, apoptosis, the process by which cells orchestrate their own demise, has been the subject of increasingly intense investigation, both from the stand-point of basic mechanisms of signal transduction and with regard to its role in normal and pathological processes in the nervous system. For the neurologist, an understanding of the mechanisms by which apoptosis determines at a cellular level the normal form of the nervous system, an appreciation of how both unchecked apoptosis and failure of enactment of the apoptotic pathway contribute to nervous system pathology and a sense of how both induction and inhibition of apoptosis can be exploited therapeutically are critical to applying the basic knowledge in this field to human disease. Early studies made it clear that substances produced by the target tissue influenced the survival of developing neurons. More recent investigations have demonstrated that they do so by influencing the production of a series of endogenous mediators and modulators of neuronal survival. Furthermore, it is evident that apoptosis is important for the development of both neuronal and non-neuronal cells in the peripheral and central nervous systems.

Animals↗

PubMed1999

Effect of polyclonal antisera developed against dense granule-associated Neospora caninum proteins on cell invasion and development in vitro by N. caninum tachyzoites.

The effects of polyclonal antisera to 2 recombinant dense granule (DG) antigens of Neospora caninum on invasion and development by N. caninum tachyzoites in baby hamster kidney cell cultures were examined. In immunofluorescent antibody tests, the anti-DG sera, at dilutions of 1:100 to 1:500, reacted intensely with individual intracellular tachyzoites and groups of tachyzoites enclosed in parasitophorous vacuoles at 2 and 52 h p.i., respectively. Tachyzoites suspended in diluted anti-DG sera and inoculated immediately into the cell cultures invaded cells in significantly fewer numbers (53-68% fewer by 2 h p.i.) than tachyzoites suspended in similarly diluted normal rabbit serum. In contrast, tachyzoites suspended in anti-Eimeria tenella sporozoite serum invaded cells as efficiently as those suspended in normal rabbit serum. Addition of anti-DG sera at the time of inoculation of tachyzoites, or to the cell cultures after the parasites had entered cells, had little effect on either the percentage or rate of their subsequent development.

Animals↗

PubMed2005

Effects of prenatal nicotine exposure on primate brain development and attempted amelioration with supplemental choline or vitamin C: neurotransmitter receptors, cell signaling and cell development biomarkers in fetal brain regions of rhesus monkeys.

Studies in developing rodents indicate that nicotine is a neuroteratogen that disrupts brain development by stimulating nicotinic acetylcholine receptors (nAChRs) that control neural cell replication and differentiation. We administered nicotine to pregnant Rhesus monkeys from gestational day 30 through 160 by continuous infusion, achieving maternal plasma levels comparable to those in smokers (30 ng/ml). Fetal brain regions and peripheral tissues were examined for nAChR subtypes, other neurotransmitter receptors, and indices of cell signaling and cell damage. Nicotine evoked nAChR upregulation, but with distinct regional disparities indicative of selective stimulatory responses. Similarly, indices of cell loss (reduced DNA), cell size and neuritic outgrowth (protein/DNA and membrane/total protein ratios) were distinct for each region and did not necessarily follow the rank order of nAChR upregulation, suggesting the involvement of additional mechanisms such as oxidative stress. We then attempted to offset the adverse effects of nicotine with standard dietary supplements known to interact with nicotine. By itself, choline elicited nicotine-like actions commensurate with its promotion of cholinergic neurotransmission. When given in combination with nicotine, choline protected some regions from damage but worsened nicotine's effects in other regions. Similarly, Vitamin C supplementation had mixed effects, increasing nAChR responses while providing protection from cell damage in the caudate, the brain region most susceptible to oxidative stress. Our results indicate that nicotine elicits neurodevelopmental damage that is highly selective for different brain regions, and that dietary supplements ordinarily thought to be neuroprotectant may actually worsen some of the adverse effects of nicotine on the fetal brain.

Adenylyl Cyclases↗

PubMed2001

Dynamic biosynthesis of heparan sulphate sequences in developing mouse brain: a potential regulatory mechanism during development.

Over recent years our understanding of the functions of the heparan sulphate (HS) family of complex polysaccharides has shifted dramatically. Once seen as simply structural scaffolding in the extracellular matrix, they are now viewed as critical players in the regulatory network of cells. They are strategically located at the cell surface and in the extracellular matrix, and there has been an increasing realization that specific sequences in the HS chains are designed for selective interactions with many proteins. Functionally, these interactions result in regulation of the protein activities. It is becoming clear that HS functions as a new class of multifunctional cell regulator. There is also growing evidence that cells can dynamically alter the structure of HS sequences that they express. Here we review recent developments and describe evidence for regulated changes in the synthesis and structure of HS chains expressed during early mouse brain development. The data suggest a new concept in which dynamic changes in biosynthesis of different HS sequences create distinct cellular HS repertoires, the heparanome. Their expression, in specific spatio-temporal patterns, is likely to endow organisms with novel regulatory mechanisms for controlling the activity of specific HS-binding proteins.

Animals↗

PubMed2001

The development of practice professional development plans from the postgraduate education allowance: a discussion of the causes and implications.

Practice professional development plans (PPDPs) began to replace the Postgraduate Education Allowance (PGEA) for general practitioners in England and Wales from April 2000. The origin of this change lies with those with educational expertise who have been concerned that the PGEA fails to encourage GPs to define their own learning needs, fails to encourage practice-based learning and fails to influence their working behaviour. The policy has been influenced however, by wider political developments which view PPDPs as a means to ensure national standards are met, to reassure the public, provide uniformity and deal with underperforming doctors. This mixture of influences has resulted in conflicting areas within PPDPs. There are different emphases on whether learning needs should be defined from the perspective of the individual or from the perspective of wider needs within the NHS. There are conflicting views about the desirability of multi- or uniprofessional learning and conflicting views about whether PPDPs are appropriate for dealing with failing doctors. PPDPs are based on a particular theory of adult learning - andragogy - which arguably fails to account for wider, richer and more significant forms of learning.

Education, Medical, Continuing↗

PubMed2003

The Caulobacter crescentus polar organelle development protein PodJ is differentially localized and is required for polar targeting of the PleC development regulator.

Regulation of polar development and cell division in Caulobacter crescentus relies on the dynamic localization of several proteins to cell poles at specific stages of the cell cycle. The polar organelle development protein, PodJ, is required for the synthesis of the adhesive holdfast and pili. Here we show the cell cycle localization of PodJ and describe a novel role for this protein in controlling the dynamic localization of the developmental regulator PleC. In swarmer cells, a short form of PodJ is localized at the flagellated pole. Upon differentiation of the swarmer cell into a stalked cell, full length PodJ is synthesized and localizes to the pole opposite the stalk. In late predivisional cells, full length PodJ is processed into a short form which remains localized at the flagellar pole after cell division and is degraded during swarmer to stalked cell differentiation. Polar localization of the developmental regulator PleC requires the presence of PodJ. In contrast, the polar localization of PodJ is not dependent on the presence of PleC. These results indicate that PodJ is an important determinant for the localization of a major regulator of cell differentiation. Thus, PodJ acts directly or indirectly to target PleC to the incipient swarmer pole, to establish the cellular asymmetry that leads to the synthesis of holdfasts and pili at their proper subcellular location.

Bacterial Proteins↗

PubMed2003

Leading the development of nursing within a Nursing Development Unit: the perspectives of leadership by the team leader and a professor of nursing.

Leadership within nursing is receiving unprecedented focus and development. This reflective narrative explores the nature of leadership, termed scholarly leadership, by an academic and a clinical leader of a Nursing Development Unit. The narrative explores the characteristics of such leadership and highlights how it empowered a nursing team to further reach its potential. Two areas, patient-centered care and the characteristics of practice, are focused upon to highlight the leadership style that the clinical leader adopted. The paper concludes by suggesting what structural and systems changes need to be put in place in order to bring about change.

Anecdotes as Topic↗

PubMed2002

Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations.

INTRODUCTION: Previous studies from our laboratory demonstrated (1) a much larger I(Ks) and (2) inability to induce early afterdepolarization (EAD) activity in epicardial and endocardial cells versus M cells. This study tests the hypothesis that these two characteristics are interrelated. METHODS AND RESULTS: Standard and floating microelectrode techniques were used to record transmembrane activity from the canine left ventricular epicardial, M, and endocardial regions in isolated tissue slices and arterially perfused wedge preparations. The I(Kr) blocker E-4031 (1 to 10 microM) caused prominent prolongation of action potential duration (APD) and induced EADs in tissues isolated from the M region, but not those from epicardium or endocardium, causing a large transmural dispersion of APD. In contrast, the I(Ks) blocker chromanol 293B (10 to 30 microM) produced moderate prolongation of APD without EADs in all three tissue types. The combination of E-4031 (1 microM) and chromanol 293B (30 microM) resulted in profound prolongation of APD and the development of EADs in all three tissue types. In the perfused wedge, neither E-4031 nor chromanol 293B alone could induce EADs. In combination, the two drugs caused significant prolongation of APD and EADs in all three transmural regions. CONCLUSION: Our results support the hypothesis that a prominent I(Ks) is responsible for the ability of epicardium and endocardium to resist some but not all of the arrhythmogenic effects of I(Kr) block. The data highlight the critical importance of I(Ks) in the canine heart and the significant role of electrotonic interactions in minimizing the development of an arrhythmogenic substrate when repolarization reserve is reduced.

Action Potentials↗

PubMed2001

The fate of developing teeth in mandibular lengthening by distraction: an experimental study.

Purpose: The purpose of this study was to observe developing teeth in a lengthened mandible after distraction. Material: Ten mongrel dogs with deciduous dentitions were used. Methods: A corticotomy was carefully made around a tooth bud and the external distractor (Orthofix M-100((R))) was connected. After a 5-day latent period, distraction was started at a rate of 0.75 mm per day for 10 consecutive days. Then, the lower jaw was stabilized by an external fixation to allow ossification. While the operation was performed on the left side (Distraction group), the contralateral side was studied for comparison (Control). In addition, a corticotomy, artificial fracture and external fixation were carried out to confirm the influence of the operation (Fracture group). Then macroscopic, radiographic and histological evaluations were carried out. Results: In the Distraction group, the space between the wall of the dental follicle and the crown expanded as distraction began. The end of the calcified root became wider and irregular during the distraction period, and finally, the apex closed. In the Fracture group, the teeth erupted although slight alterations of the root shape were observed in association with the operation period. Conclusion: The root became irregular, but the teeth erupted within the distraction area. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.

Journal Article↗