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PubMed1999

Structural characterization of two tandemly arranged DNA methyltransferase genes from Neisseria gonorrhoeae MS11: N4-cytosine specific M.NgoMXV and nonfunctional 5-cytosine-type M.NgoMorf2P.

Two adjacent genes encoding DNA methyltransferases (MTases) of Neisseria gonorrhoeae MS11, an active N4-cytosine specific M. NgoMXV and an inactive 5-cytosine type M. NgoMorf2P, were cloned into Escherichia coli and sequenced. We analyzed the deduced amino acid sequence of both gene products and localized conserved regions characteristic for DNA MTases. Structure prediction, threading-derived alignments, and comparison with the common fold for DNA MTases allowed for construction of super-secondary and tertiary models for M.NgoMorf2P and M.NgoMXV, respectively. These models helped in identification of amino acids and structural elements essential for function of both enzymes. The implications of this putative structural model on the catalytic mechanism of M.NgoMXV and its possible relation to the common ancestor of modern DNA amino-MTases are also discussed.

Amino Acid Sequence↗

PubMed1996

Fibroblast growth factor-2 stimulates embryonic cardiac mesenchymal cell proliferation.

The proliferation response of stage 36 chick atrioventricular valve mesenchymal cells to fibroblast growth factor-2 (FGF-2) was studied in the tissue-like environment of three-dimensional cell aggregates maintained in organ culture. The mitogenic effects of FGF-2 on mesenchymal tissue depended on the FGF-2-stimulated formation of a fibronectin-containing extracellular matrix. The matrix was absent in unstimulated aggregates, and co-localized with regions of actively proliferating cells in stimulated aggregates. Inhibition of fibronectin matrix formation by the inclusion of Arg-Gly-Asp-containing peptides, which compete with fibronectin for binding to the cell surface alpha 5 beta 1 integrin receptors, abolished the proliferation effects of FGF-2. Inhibition of sulfation of cell surface glycosaminoglycans by treatment with sodium chlorate significantly reduced both the formation of the fibronectin matrix and cell proliferation in response to FGF-2, suggesting an involvement of the low-affinity sulfated glycosaminoglycan FGF receptor system. Thus, the FGF-stimulated growth of embryonic atrioventricular valve mesenchyme in vitro involves the production of a fibronectin matrix. We suggest that the stimulation of the fibronectin matrix represents an essential element in growth factor signaling of mesenchymal tissue, with the matrix serving as an anchorage substratum for the proliferating cells.

Animals↗

PubMed1997

Expression of smooth muscle alpha-actin in mesenchymal cells during formation of avian endocardial cushion tissue: a role for transforming growth factor beta3.

During early cardiac morphogenesis, outflow tract (OT) and atrio-ventricular (AV) endothelial cells differentiate into mesenchymal cells, which have characteristics of smooth muscle-like myofibroblasts, and which form endocardial cushion tissue, the primordia of valves, and septa in the adult heart. During this embryonic event, transforming growth factor beta3 (TGF beta3) is an essential element in the progression of endothelial-transformation into mesenchyme. TGF beta(s) are known to be a potent inducer for mesodermal differentiation and a promoter for differentiation of endothelial cells into smooth muscle-like cells. Using a monoclonal antibody against smooth muscle-specific alpha-actin (SMA), we examined the immunohistochemical staining of this form of actin in avian endocardial cushion tissue formation. To determine whether TGF beta3 initiates the expression of SMA, the pre-migratory AV endothelial monolayer was cultured with or without chicken recombinant TGF beta3 and the expression of SMA was examined immunochemically. Migrating mesenchymal cells expressed SMA beneath the cell surface membrane. These cells showed a reduction of endothelial specific marker antigen, QH1. Stationary endothelial cells did not express SMA. The deposition of SMA in the mesenchymal tissue persisted until the end of the fetal period. Pre-migratory endothelial cells cultured in complete medium (CM199) that contained TGF beta3 expressed SMA, whereas cells cultured in CM199 alone did not. At the onset of the endothelial-mesenchymal transformation, migrating mesenchymal cells express SMA and the expression of this form of actin is upregulated by TGF beta3. The induction of the expression of SMA by TGF beta3 is one of the initial events in the cytoskeletal reorganization in endothelial cells which separate from one another during the initial phenotypic change associated with the endothelial-mesenchymal transformation.

Actins↗

PubMed1997

Timing of edentulation and extraction in the management of oral cavity and oropharyngeal malignancies.

BACKGROUND: Pretreatment dental evaluation is an essential element in the management of the head and neck cancer patient. Frequently, the dental condition requires edentulation or multiple extractions prior to radiotherapy. These extractions may be carried out at the time of oncologic resection. Such practice is routine for some surgeons but resisted by others who fear increased postoperative wound complications. To date, no study evaluating the safety and efficacy of extractions at the time of surgical resection has been reported. This paper retrospectively examines the postoperative course of head and neck cancer patients with varying strategies of dental management. METHODS: Retrospective analysis of patients with surgically treated oral cavity or oropharyngeal malignancies and dental extractions or edentulation at a tertiary oncology center from 1985 to 1994 was made. Postoperative wound infection, fistula, and length of stay data were compared for patients undergoing concurrent extraction and those having dental extractions in the postoperative period. RESULTS: Thirty-two patients underwent ablative resection with concurrent extraction, whereas 23 had postsurgical extractions. The infection and fistula rates were 16% and 9% in the concurrent group and 35% and 26% for patients having postsurgical extractions. Mean postoperative stays were significantly shorter for patients undergoing concurrent extraction (15 +/- 8 days) compared with those of the postsurgical group (27 +/- 14 days). CONCLUSIONS: Patients whose extractions were performed concurrent with the oncologic resection experienced fewer postoperative wound complications and had significantly shorter postoperative hospitalizations than did the postsurgical group.

Female↗

PubMed1998

Studies on the genotoxicity of molybdenum salts in human cells in vitro and in mice in vivo.

Molybdenum is an essential element in plants and animals as a cofactor for enzymes. Molybdenum trioxide is used in metallurgical processes, in cosmetics as a pigment, and in contact lens solution, yet limited information is available on molybdenum genotoxicity. In the present study the micronucleus (MN) assay in human lymphocytes and mouse bone marrow and the dominant lethal assay in mice were used to assess the genotoxic effects of molybdenum salts in vitro and in vivo. Two salts of molybdenum were tested in whole blood cultures. Ammonium molybdate was more potent than sodium molybdate in causing a dose-dependent decrease in viability and replicative index and an increase in MN formation in binucleated lymphocytes (P < 0.001). A dose-response in both kinetochore-positive MN (caused by chromosome lagging) and kinetochore-negative MN (associated with chromosome breakage) was observed. Based on the results of a toxicity study of sodium molybdate, two doses, 200 and 400 mg/kg, were assessed in the bone marrow MN assay in mice (two i.p. injections 24 and 48 hr prior to euthanasia). A modest but statistically significant increase in MN frequency in polychromatic erythrocytes was observed (P < 0.05). The same treatment protocol was used to analyze dominant lethality. A dose-dependent increase in postimplantation loss represented mostly by early resorptions was observed the first week after treatment (P = 0.003). These preliminary data suggest that sodium molybdate induces dominant lethality at the postmeiotic stage of spermatogenesis. Overall, molybdenum salts produced moderately positive results both in vitro in human cells and in vivo in mice.

Adult↗

PubMed1998

Content of dolichol and retinol in isolated rat non-parenchymal liver cells.

The liver sinusoids, that are considered as a functional unit, harbour four types of sinusoidal cells (Ito, Kupffer, endothelial and pit cells). Dolichol content has been determined in many tissues and subcellular compartments, alteration has been reported in many types of liver injury, but until now no data are available on its content in every type of sinusoidal non-parenchymal liver cells. Dolichol and retinol metabolism might intersect in their traffic in biological membranes. Intercellular as well as intracellular exchange of retinoids is an essential element of important processes occurring in liver cells. It has been suggested that the role of dolichol, besides being a carrier of oligosaccharides in the biosynthesis of N-linked glycoproteins, may be to modify membrane fluidity and permeability, and facilitate fusion of membranes. Dolichol in the membrane is intercalated between the two-halves of the phospholipid bilayer, but its exact disposition is not known and the movement and distribution of retinoid in membranes may vary with the geometry of the membranes. Therefore the aim of this study is to obtain a global understanding of the sinusoidal system regarding dolichol and retinol content in each type of isolated rat liver sinusoidal cell, in normal conditions and after vitamin A administration. The information that can be drawn from the present results is that with normal vitamin A status of the animal, the dolichol content is almost uniform in all liver cells. After vitamin A supplementation, a great increase of dolichol, together with the known increase of retinol, can be measured only in a subpopulation of the Ito cells, the Ito-1 subfraction. Therefore in the cells that are present in the hepatic sinusoid, different pools of dolichol may have separate functions. Because retinol traffic among cells, membranes and plasma still remains to be fully understood, roles of dolichol in the exchange of vitamin A among sinusoidal liver cells are discussed.

Animals↗

PubMed1998

Peptide siderophores.

Siderophores are low molecular weight iron chelators, produced by virtually all bacteria, fungi and some plants. They serve to deliver the essential element iron, barely soluble under aerobic conditions, into microbial cells. Siderophores are therefore important secondary metabolites which are very often based on amino acids and their derivatives. Biosynthesis, transport, regulation and chemical synthesis of natural siderophores and their analogues is of considerable interest for the protein and peptide chemist. This review gives an overview of the structural classes of peptidic siderophores, along with data on their biosynthesis. On a number of representative examples, strategies and schemes of their chemical synthesis are described.

Amino Acid Sequence↗

PubMed2000

Hyperthermia by MR-guided focused ultrasound: accurate temperature control based on fast MRI and a physical model of local energy deposition and heat conduction.

Temperature regulation in MR-guided focused ultrasound requires rapid MR temperature mapping and automatic feedback control of the ultrasound output. Here, a regulation method is proposed based on a physical model of local energy deposition and heat conduction. The real-time evaluation of local temperature gradients from temperature maps is an essential element of the control system. Each time a new image is available, ultrasound power is adjusted on-the-fly in order to obtain the desired evolution of the focal point temperature. In vitro and in vivo performance indicated fast and accurate control of temperature and a large tolerance of errors in initial estimates of ultrasound absorption and heat conduction. When using correct estimates for the physical parameters of the model, focal point temperature was controlled within the measurement noise limit. Initial errors in absorption and diffusion parameters are compensated for exponentially with a user-defined response time, which is suggested to be on the order of 10 sec.

Animals↗

PubMed2001

Toxicology of choroid plexus: special reference to metal-induced neurotoxicities.

The chemical stability in the brain underlies normal human thinking, learning, and behavior. Compelling evidence demonstrates a definite capacity of the choroid plexus in sequestering toxic heavy metal and metalloid ions. As the integrity of blood-brain and blood-CSF barriers, both structurally and functionally, is essential to brain chemical stability, the role of the choroid plexus in metal-induced neurotoxicities has become an important, yet under-investigated research area in neurotoxicology. Metals acting on the choroid plexus can be categorized into three major groups. A general choroid plexus toxicant can directly damage the choroid plexus structure such as mercury and cadmium. A selective choroid plexus toxicant may impair specific plexus regulatory pathways that are critical to brain development and function, rather than induce massive pathological alteration. The typical examples in this category include lead-induced alteration in transthyretin production and secretion as well as manganese interaction with iron in the choroid plexus. Furthermore, a sequestered choroid plexus toxicant, such as iron, silver, or gold, may be sequestered by the choroid plexus as an essential CNS defense mechanism. Our current knowledge on the toxicological aspect of choroid plexus research is still incomplete. Thus, the future research needs have been suggested to focus on the role of choroid plexus in early CNS development as affected by metal sequestration in this tissue, to explore how metal accumulation alters the capacity of the choroid plexus in regulation of certain essential elements involved in the etiology of neurodegenerative diseases, and to better understand the blood-CSF barrier as a defense mechanism in overall CNS function.

Animals↗

PubMed2001

Are distinctive ethical principles required for cluster randomized controlled trials?

Cluster randomized trials are increasingly used in research into health care and health services. Ethics of individual patient randomized trials have been elucidated in a number of different codes, but less attention has been given to the ethical issues raised by cluster randomized trials. I assess the challenges raised by cluster randomized controlled trials by considering three questions: What are the essential elements of ethical medical research, particularly experiments on people? What are the features which distinguish cluster randomized controlled trials from ordinary RCTs? Do the distinctive features of cluster randomized trials entail new ethical principles, or careful application of existing principles? I conclude that cluster randomized controlled trials raise new issues on the nature and practice of informed consent, because of the levels at which consent can be sought, and for which it can be sought. In addition, careful consideration of the principles relating to the quality of the scientific design and analysis, balance of risk and benefit, liberty to leave a trial, early stopping of a trial and the power to exclude people from potential benefits is required.

Cluster Analysis↗

PubMed2001

Terminologia anatomica: considered from the perspective of next-generation knowledge sources.

This report examines the semantic structure of Terminologia Anatomica, taking one page as an example. The focus of analysis is the meaning imparted to an anatomical term by virtue of its location within the structured list. Terminologia's structure, expressed through hierarchies of headings, varied typographical styles, indentations, and an alphanumeric code, implies specific relationships among the terms embedded in the list. Together, terms and relationships can potentially capture essential elements of anatomical knowledge. The analysis focuses on these knowledge elements and evaluates the consistency and logic in their representation. Most critical of these elements are class inclusion and part-whole relationships. Since these are implied, rather than explicitly modeled, by Terminologia, the use of the term list is limited to those who have some knowledge of anatomy; computer programs are excluded from navigating through the terminology. Assuring consistency in the explicit representation of anatomical relationships would facilitate adoption of Terminologia as the anatomical standard by the various controlled medical terminology (CMT) projects. These projects are motivated by the need to computerize the patient record, and their aim is to generate machine-understandable representations of biomedical concepts, including anatomy. Because of the lack of a consistent and explicit representation of anatomy, each of these CMTs has generated its own anatomy model. None of these models is compatible with any other, yet each is consistent with textbook descriptions of anatomy. The analysis of the semantic structure of Terminologia Anatomica leads to some suggestions for enhancing the term list in ways that would facilitate its adoption as the standard for anatomical knowledge representation in biomedical informatics.

Anatomy↗

PubMed2001

Decision aids for people facing health treatment or screening decisions.

BACKGROUND: Decision aids are interventions designed to help people make specific and deliberative choices among options (including status quo) by providing (at a minimum) information on the options and outcomes relevant to a person's health status. A systematic review is needed to summarize what is known about their efficacy. OBJECTIVES: 1. To create an inventory of existing decision aids. 2. To conduct a systematic review of randomized controlled trials of decision aids aimed at improving people's decision making and outcomes. SEARCH STRATEGY: The following electronic databases were searched: MEDLINE, EMBASE, PsycINFO, CINAHL, Aidsline, Cancerlit, the Cochrane Controlled Trials Register. In addition, individuals known to be active in the field of decision support were contacted. SELECTION CRITERIA: We screened titles and abstracts for all interventions providing structured, detailed, and specific information on treatment or screening options and outcomes to aid decision making. Information about the decision aids was compiled in an inventory and those evaluated in a randomized controlled trial were reviewed in detail. DATA COLLECTION AND ANALYSIS: Using Cochrane review methods, two reviewers independently screened and extracted data on several evaluation criteria. Results of randomized trials were pooled using weighted mean differences and relative risks with all data analysed using a random effects model. MAIN RESULTS: Eighty-seven decision aids were identified. Twenty-three of them had been evaluated in 24 randomized controlled trials. Among the trials comparing decision aids to usual care interventions, decision aids performed better in terms of: a) greater knowledge of options in seven of seven studies (weighted mean difference (WMD = 19 out of 100, 95% confidence interval (CI): 13,25); b) more realistic expectations in two of three studies (RR=1.48 95%CI 1.02, 2.14); c) lower decisional conflict related to feeling informed in three of three studies (WMD = -9.0 of 100 95%CI: -15, -3); d) reducing the proportion of people who were passive in decision making in three of four studies (RR = 0.63, 95% CI: 0.5, 0.8). When simpler decision aids were compared to more detailed ones, the relative improvement was significant in: a) improved knowledge in two of seven studies (WMD = 4 out of 100, 95% CI: 2, 5); b) realistic expectations in two of two studies (relative risk (RR ranged from 1.5 95%CI: 1.3,1.8); and c) decisional conflict in one of two studies (WMD= -4 95% CI -8,-0.2). There was a consistent trend for decision aids to do no better than comparison interventions in affecting: satisfaction with the decision in five of six studies, satisfaction with the decision making process in four of five studies, and anxiety in four of five studies. Decision aids had a variable effect on which screening or treatment options were selected. Exposure to decision aids relative to controls resulted in a consistent non-significant trend toward reduced preference for major surgery over conservative options by 21 to 42 per cent in five of five studies; however, they had no impact on circumcision in two of two studies. For colon and prostate cancer screening choices, the results were inconsistent. Two studies have shown no impact on persistence with chosen option and few studies have shown significant benefits on general health outcomes (two of three studies), or disease-specific health outcomes (one of four studies). REVIEWER'S CONCLUSIONS: The number of decision aids is expanding, but there is considerable overlap in some areas leaving gaps in others. Trials of decision aids indicate that they are superior to usual care interventions in improving knowledge and realistic expectations of the benefits and harms of options; reducing passivity in decision making; and lowering decisional conflict stemming from feeling uninformed. When simpler versions of decision aids are compared to more detailed aids, the differences in knowledge are marginal but there are other benefits in terms of creating realistic expectations and in reducing decisional conflict. To date, decision aids have had little effect on anxiety or satisfaction with the decision making process or satisfaction with the decision. Their effects on choices vary with the decision. The effects on persistence with chosen therapies and health outcomes require further evaluation. The essential elements in decision aids for different groups and different types of decisions need to be established. Consensus needs to be reached regarding standards for developing and evaluating decision aids.

Decision Support Techniques↗

PubMed2002

Chemical strategies for iron acquisition in plants.

Iron is an essential element for plant nutrition. Although iron is the fourth most abundant element (3 %) of the earth's crust, it is not readily available because of its low solubility. Therefore, plants need an active mechanism to extract iron from the soil. They have evolved several chemical strategies to acquire iron ions and the physiology of these mechanisms has been known for a long time. Only recently, the use of molecular genetic approaches has led to a biochemical and molecular characterization of the players involved, thus providing an entry to the manipulation of iron uptake in plants.

Arabidopsis↗

PubMed1983

Immunopathogenesis of experimental Chagas' disease in mice: damage to the autonomic nervous system.

Infection of mice with Trypanosoma cruzi produces pathological change which in many ways parallels the evolution of Chagas' disease in human patients. An essential element in this experimental pathology is the intense denervation observed during the resolution of acute-stage parasitaemia. Host cells, from a variety of tissues, have been shown to absorb parasite antigens and thus to become targets for the hosts' own anti-parasite immune response. The definition of common antigenic determinants, shared by T. cruzi and human neuronal cells, might explain why the electrical conduction systems and the autonomic nervous system are especially vulnerable to the postulated autoimmune process. We have the models, the tools and the hypotheses, and now we await the proof.

Animals↗

PubMed1991

Spontaneous decidual reactions and menstruation in the black mastiff bat, Molossus ater.

Uterine function was assessed histologically in nonpregnant Molossus ater removed from a laboratory breeding colony. During the luteal phase of the cycle, bilateral decidual reactions were found to develop spontaneously in the absence of either embryos or experimental manipulation of the uterus. These included the formation of early decidual giant cells, closure of the uterine lumina, and morphological changes in the endometrial blood vessels. Some endothelial cell hypertrophy was noted in much of the decidua, but this was most pronounced in vessels associated with an unusual vascular tuft that formed in the endometrium surrounding the cranial end of the uterine lumen. These latter vessels also developed very prominent basal laminae. In pregnant bats, this tuft played a central role in the morphogenesis of the definitive discoidal chorioallantoic placenta. At the end of nonpregnant cycles, the decidua became necrotic and was sloughed off with associated bleeding. As in menstruating catarrhine primates, the endometrium of M. ater is vascularized by spiral arterioles and populated by distinctive granulocytes containing large, acidophilic granules. Increased coiling of these arterioles did not appear to be an essential element in the mechanism of mensturation in this species. M. ater is a monotocous, seasonal breeder, with a relatively long gestation period. Although it has a bicornuate uterus, ovulation and implantation appear to occur only on the right side of the tract. The ability to menstruate probably affords this bat an efficient mechanism for eliminating a highly differentiated endometrium from the usual implantation site in the event of a reproductive failure. In the wild, this may provide M. ater with another chance to establish a pregnancy at a still opportune time during the same breeding season.

Animals↗

PubMed1980

Failure of rats to escape from a potentially lethal microwave field.

Ocularly pigmented rats, all mature females of the Long-Evans strain, were repeatedly presented an opportunity to escape from an intense 918-MHz field (whole-body dose rate = 60 mW/g) to a field of lower intensity (40, 30, 20, or 2 mW/g) by performing a simple locomotor response. Other rats could escape 800-microamperemeter faradic shock to the feet and tail by performing the same response in the same milieu, a multimode cavity. None of 20 irradiated rats learned to associate entry into a visually well-demarcated area of the cavity with immediate reduction of dose rate, in spite of field-induced elevations of body temperature to levels that exceeded 41 degrees C and would have been lethal but for a limit on durations of irradiation. In contrast, all of ten rats motivated by faradic shock rapidly learned to escape. The failure of escape learning by irradiated animals probably arose from deficiencies of motivation and, especially, sensory feedback. Whole-body hyperthermia induced by a multipath field may lack the painful or directional sensory properties that optimally promote the motive to escape. Moreover, a decline of body temperature after an escape-response-contingent reduction of field strength will be relatively slow because of the large thermal time constants of mammalian tissues. Without timely sensory feedback, which is an essential element of negative reinforcement, stimulus-response associability would be imparied, which could retard or preclude learning of an escape response.

Animals↗

PubMed1999

[Not Available].

The emergence of a 'norm of normalcy' in 19th century laboratories and hospitals was in no way simply a byproduct of the scientific search for knowledge. It was instead closely associated with expectations of social egalitarianism which merged with the moral economy of a new scientific objectivity. The establishment of normal people as a valid measure for a population socially divided and segregated in estates was thus an essential element of the processes of social formulation which created our modern society.

Health Status↗

PubMed2006

Molecular and cellular organization of insect chemosensory neurons.

Animals use their chemosensory systems to detect and discriminate among chemical cues in the environment. Remarkable progress has recently been made in our knowledge of the molecular and cellular basis of chemosensory perception in insects, based largely on studies in Drosophila. This progress has been possible due to the identification of gene families for olfactory and gustatory receptors, the use of electro-physiological recording techniques on sensory neurons, the multitude of genetic manipulations that are available in this species, and insights from several insect model systems. Recent studies show that the superfamily of chemoreceptor proteins represent the essential elements in chemosensory coding, endowing chemosensory neurons with their abilities to respond to specific sets of odorants, tastants or pheromones. Investigating how insects detect chemicals in their environment can show us how receptor protein structures relate to ligand binding, how nervous systems process complex information, and how chemosensory systems and genes evolve.

Animals↗