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PubMed1980

Periodic ACTH discharge.

A 9 1/2-year-old girl is presented who had cyclical attacks of abdominal pain, vomiting, emotional disturbance, and marked weight change for two years. Associated findings were facial plethora, hypertension, transient hyperglycemia and glycosuria, elevated plasma ACTH, cortisol, and urinary 17-OHCS excretion, and low plasma osmolality with hyponatremia. Urinary excretion of catecholamines and porphyrin metabolites was not increased. Between episodes, she showed no abnormal clinical signs or laboratory data. The attacks were effectively suppressed with the administration of chlorpromazine. The disorder appears to be due to the periodic release of excessive ACTH; the cause remains unknown.

Adrenocortical Hyperfunction↗
PubMed2003

Control of spatially heterogeneous and time-varying cellular reaction networks: a new summation law.

A hallmark of a plethora of intracellular signaling pathways is the spatial separation of activation and deactivation processes that potentially results in precipitous gradients of activated proteins. The classical metabolic control analysis (MCA), which quantifies the influence of an individual process on a system variable as the control coefficient, cannot be applied to spatially separated protein networks. The present paper unravels the principles that govern the control over the fluxes and intermediate concentrations in spatially heterogeneous reaction networks. Our main results are two types of control summation theorems. The first type is a non-trivial generalization of the classical theorems to systems with spatially and temporally varying concentrations. In this generalization, the process of diffusion, which enters as the result of spatial concentration gradients, plays a role similar to other processes such as chemical reactions and membrane transport. The second summation theorem is completely novel. It states that the control by the membrane transport, the diffusion control coefficient multiplied by two, and a newly introduced control coefficient associated with changes in the spatial size of a system (e.g., cell), all add up to one and zero for the control over flux and concentration. Using a simple example of a kinase/phosphatase system in a spherical cell, we speculate that unless active mechanisms of intracellular transport are involved, the threshold cell size is limited by the diffusion control, when it is beginning to exceed the spatial control coefficient significantly.

Animals↗
PubMed2006

Triclosan loaded ureteral stents decrease proteus mirabilis 296 infection in a rabbit urinary tract infection model.

PURPOSE: Infection and encrustation remain major limitations of ureteral stent use and to our knowledge no device has completely overcome these obstacles to date. Triclosan is a biocide currently used in a plethora of consumer and medical products that has recently been loaded into a ureteral stent. Using a rabbit model of UTI we examined the effects of triclosan impregnated stent segments on the growth and survival of Proteus mirabilis, a uropathogen commonly associated with device related UTI and encrustation. MATERIALS AND METHODS: A total of 48 male New Zealand White rabbits were instilled transurethrally with 1 x 10(6) P. mirabilis 296. A stent curl from a triclosan eluting, Percuflex Plus or Optima ureteral stent was placed intravesically. Urine was cultured on days 1, 3 and 7. On day 7 the stents were assessed for encrustation and viable organisms, while the bladders were scored for the degree of inflammation. RESULTS: Throughout the study urine isolated from the triclosan group contained significantly fewer viable organisms than controls with 7 of 13 animals completely clearing the infection by day 7. Similarly 9 of 13 triclosan eluting stents showed no viable organisms upon recovery and the remaining 4 showed significantly fewer organisms than controls. Urine and stents in all controls were positive for P. mirabilis at all time points. Although there was no significant difference in encrustation among the groups, bladders harvested from the triclosan group demonstrated significantly less inflammation. CONCLUSIONS: Triclosan eluting stents greatly decreased P. mirabilis growth and survival in a rabbit UTI model compared to controls. These stents may prove useful for decreasing device related P. mirabilis UTIs.

Animals↗
PubMed1996

Emerging paradigms in granulocyte-macrophage colony-stimulating factor signaling.

The myelomonocytic lineage of hematopoiesis is regulated by the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). This cytokine has proven to be safe for use in coordination with the treatments for bone marrow transplants and acute myelogenous leukemia. GM-CSF and related cytokines operate through specific receptors in the membranes of target cells of the myelopoietic lineages (both immature and mature cells). The exact signal transduction mechanisms in the cell are only beginning to be clarified and involve a plethora of signaling molecules. With a wealth of new information from studies in GM-CSF-induced cell activation, three major experimental approaches are emerging as gold standards in the exploration of those signaling pathways initiated by hematopoietic growth factors. We consider here: (1) a protein-protein interaction, as exemplified by the association between the cytokine membrane receptor and JAK kinase; (2) a covalent modification of an enzyme, as studied in the phosphorylation of MAP kinase; and (3) a protein-DNA interaction, as demonstrated by the translocation of STAT from the cytosol to the nucleus where it can bind to the promoters of specific genes.

DNA-Binding Proteins↗
PubMed1984

Cataracts and cataract operations (1).

Cataract operations are commonly performed in either a primary-care or a tertiary-care center. A plethora of information (some of which is unfounded) has been disseminated in the lay news media about the advances in the surgical techniques of cataract removal. This article reviews some of the recent concepts about the formation of cataracts and the modern approaches for their extraction. It is directed at the nonophthalmologic primary-care physician who refers patients for evaluation or performs the ancillary tests in preparation for a cataract operation. Space limitations prevent a complete review of the subject. Some of the controversial aspects of cataract surgical procedures are addressed objectively, but bias is unavoidable.

Adult↗
PubMed1994

The biology of the artery wall in atherogenesis.

A great deal of progress has been made in the past few years in our understanding of the processes involved in atherogenesis and in mechanisms by which commonly accepted risk factors may affect these processes. These insights have allowed us to understand how various interventions may retard atherogenesis and decrease clinical events by improving plaque stability. The identification of new risk factors, such as lipoprotein(a), and of particular molecules that can be identified in atherosclerotic tissue, such as adhesion molecules, growth factors, cytokines, and proteins that regulate cholesterol uptake and removal, have identified several potential new targets for therapeutic intervention. Advances in molecular biologic techniques, including transgenic techniques, have markedly increased the types of potential interventions available. A major challenge for the future will be to determine which among this plethora of therapeutic possibilities holds the most promise for decreasing the morbidity and mortality associated with this disease.

Animals↗
PubMed2000

Absence of mutations in the functional domains of the human MDM2 oncogene in non-small cell lung carcinomas.

Increasing evidence suggests that MDM2 oncoprotein participates in a complex array of interactions with a plethora of molecules, including cell-cycle and transcriptional regulators, as well as determinants of the cell differentiation and senescence. The tumorigenic potential of MDM2 is mainly determined by overexpression due to gene amplification, mRNA overexpression and possibly translational enhancement. Although artificially created mutations have been demonstrated to abolish normal MDM2 function, there is little information concerning its mutational status in human tissues. In this study, we screened all the functional domains of MDM2 for mutations in a series of 58 non-small cell lung carcinomas (NSCLCs), but none was found. Therefore, we report that MDM2 mutations are an extremely rare phenomenon of non-small cell lung carcinogenesis. A putative explanation for this observation may be the labyrinth of interactions necessary for cell viability, in which MDM2 takes part, a finding also supported by its stringent interspecies conservation.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

The selective mGlu2/3 receptor agonist LY354740 attenuates morphine-withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal.

Naltrexone-precipitated morphine withdrawal induces hyperactivity of locus coeruleus (LC) neurons, as well as a plethora of behavioral withdrawal signs. Previous research has demonstrated that an increased release of glutamate and activation of AMPA receptors, particularly in the LC, play an important role in opiate withdrawal. LY354740 is a novel Group II metabotropic glutamate mGlu2/3 receptor agonist that decreases the release of glutamate. Therefore, we investigated the effect of LY354740 on naltrexone-precipitated morphine-withdrawal-induced activation of LC neurons and behavioral signs of morphine withdrawal. In in vivo recordings from anesthetized rats, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently attenuated the morphine-withdrawal-induced activation of LC neurons. In unanesthetized, morphine-dependent animals, pretreatment with LY354740 (3-30 mg/kg, s.c.) dose-dependently suppressed the severity and occurrence of many naltrexone-precipitated morphine-withdrawal signs. These results indicate mGlu2/3 receptor agonists: (1) can attenuate the morphine-withdrawal-induced activation of LC neurons and many behavioral signs of morphine withdrawal; and (2) may have therapeutic effects in man for the treatment of opiate withdrawal.

Analysis of Variance↗
PubMed2003

Anxiety disorders: treatment considerations.

Anxiety disorders are among the most prevalent and disabling psychiatric disorders. Today patients have a plethora of treatment options to manage these potentially disabling and costly psychiatric disorders. Anxiety disorders represent a large portion of primary care visits and diverse practice settings. Nurses are in key positions to identify symptoms of various anxiety disorders, initiate appropriate treatment, or refer patients for treatment. Families play a key role in successful treatment planning and must be an integral part of the health care team. Major nursing interventions must focus on making an accurate diagnosis, initiating appropriate treatment, and facilitating a higher level of functioning and quality of life.

Anxiety Disorders↗
PubMed2000

Before Kubler-Ross: lessons about grief from the book of Job.

Medicine is as old as the human species, and medical literature is among the earliest writing. Current research is of great help in identifying new interventions, but a great deal of the art of medicine is showcased in ancient works. The 20th century saw a plethora of books, articles, and monographs on the subjects of grief, death and dying, and suffering, but none of these has provided greater insight than the biblical book of Job. Excerpts from Job illustrate both the nature of grief and appropriate intervention when it is confronted.

Bible↗
PubMed2000

Endoscopic versus traditional approaches to choanal atresia.

With the introduction of endoscopic techniques and powered instrumentation for pediatric sinusitis, one would expect that the definitive treatment of congenital choanal atresia has been established. An international survey of pediatric otolaryngologists and the plethora of surgical approaches in the literature, however, indicate that there is still much controversy in its management. This article addresses this controversy between endoscopic and traditional approaches to neonatal bilateral bony choanal atresia and proposes guidelines for optional treatment.

Child, Preschool↗
PubMed2001

Estrogen receptor antibodies: specificity and utility in detection, localization and analyses of estrogen receptor alpha and beta.

The role of estrogens in regulating cellular metabolism in many tissues is well documented. Estrogens regulate cellular activity by interacting with specific intracellular receptor proteins. Two estrogen receptor (ER) isoforms have been isolated, cloned and characterized. Estrogen receptor alpha (ERalpha) and beta (ERbeta) are ligand dependent transcriptional activators, which regulate gene expression via complex mechanisms requiring ligand binding, transformation, dimerization, and interaction with specific unique cis DNA hormone response elements (EREs) and co-activators and co-repressors. Studies of ER structure and function have been tremendously facilitated by the development of molecular and biologic probes. Cloning and functional studies of the ERalpha and ERbeta have delineated some of the structural requirements involved in receptor function. Immunochemical analyses together with biochemical and molecular approaches have contributed to our understanding of ER structure and function. Although antibodies to ER have been developed and utilized for the past two decades, there has yet to be a comprehensive review that discusses the utility and usefulness of these antibodies in receptor detection and analysis. In this review, we summarize a plethora of information concerning the development and characterization of site-directed monoclonal and polyclonal antibodies to the ERalpha and ERbeta. We provide critical discussion on the characteristics and utility of ER antibodies in analyses, characterization and localization of ER isoforms in various tissues. We also provide a comparison of the potential utility of the available antibodies in various immunochemical assays. An epitope map detailing the specific sites of antibody-receptor interactions is constructed based on the available information. The advent of antibodies with high specificity and titer had facilitated detection of ER isoforms in normal and neoplastic tissues. The advent of new antibodies remains a powerful tool for assessment of ER expression and post-translational modification and receptor function in many experimental systems.

Antibodies, Monoclonal↗
PubMedDate not supplied

Different shapes of the steroid hormone 1alpha,25(OH)(2)-vitamin D(3) act as agonists for two different receptors in the vitamin D endocrine system to mediate genomic and rapid responses.

Vitamin D(3) produces biologic responses as a consequence of its metabolism into 1alpha,25(OH)(2)-vitamin D(3) [1alpha,25(OH)(2)D(3)] and 24R,25(OH)(2)-vitamin D(3). The metabolic production of these two seco steroids and their generation of the plethora of biologic actions that are attributable to the parent vitamin D(3) are orchestrated via the integrated operation of the vitamin D endocrine system. This system is very similar in its organization to that of classic endocrine systems and is characterized by an endocrine gland (the kidney, the source of the two steroid hormones), target cells which possess receptors for the steroid hormones, and a feed-back loop involving changes in serum Ca(2+) that alter the secretion of parathyroid hormone (a stimulator of the renal 1-hydroxylase) which modulates the output by the kidney of the steroid hormones. There are, however, at least two unique aspects to the vitamin D endocrine system. (a) The chemical structures of vitamin D and its steroid hormones dictate that these be highly conformationally flexible molecules present a wide variety of shapes to their biologic environments. (b) It is now believed that 1alpha,25(OH)(2)D(3) produces biologic responses through two distinct receptors which recognize totally different shapes of the conformationally flexible 1alpha,25(OH)(2)D(3). Thus, the classic actions of 1alpha,25(OH)(2)D(3) to regulate gene transcription occur as a consequence of the stereospecific interaction of a modified 6-s-trans bowl-shape of 1alpha,25(OH)(2)D(3) with its nuclear receptor (VDR(nuc)). The ability of 1alpha,25(OH)(2)D(3) to generate a variety of rapid (seconds to minutes) biologic responses (opening of chloride channels, activation of PKC and MAP kinases) requires a planar 6-s-cis ligand shape which is recognized by a putative plasma membrane receptor (VDR(mem)) to initiate appropriate signal transduction pathways. This report summarizes the evidence for the specificity of different ligand shapes and the operation of the two receptor families for 1alpha,25(OH)(2)D(3).

Animals↗
PubMed1992

Laser therapy of colorectal carcinoma.

A plethora of literature is available demonstrating the efficacy of Nd:YAG laser therapy for obstructing or bleeding colorectal cancers. The in-hospital mortality and morbidity rates can be reduced when Nd:YAG laser therapy is used to avoid operative diversion prior to resection and anastomosis. The Nd:YAG laser used to control bleeding or obstruction in those patients with either widely metastatic or unresectable locoregional disease has been successful in the majority of patients and has been associated with minimal morbidity and mortality rates. This laser may be the only treatment modality that may substitute for operative diversion in hopeless clinical situations such as hemorrhage or obstruction in patients with advanced disease. The utility of photodynamic therapy for colorectal cancer will require definition in further controlled trials.

Carcinoma↗
PubMed2003

Spatial mechanisms for coexistence of species sharing a common natural enemy.

We examine the conditions under which spatial structure can mediate coexistence of apparent competitors. We use a spatially explicit, host-parasitoid metapopulation model incorporating local dynamics of Nicholson-Bailey type and global dispersal. Depending on the model parameters, the resulting system displays a plethora of asynchronous dynamical behaviors for which permanent or transient coexistence is observed. We identify a number of spatially mediated tradeoffs which apparent competitors can utilize and demonstrate that the dynamics of spatial coexistence can typically be understood from consideration of two and three patch systems. The phase relationships of species abundances are different for our model than for some other mechanisms of spatial coexistence. We discuss the implications of our findings relative to issues of community organization and biological conservation.

Animals↗
PubMed2001

Cone venom--from accidental stings to deliberate injection.

Cone snails have long been of note due to their colorful shells and deadly venom. Over the years, a number of people who have encountered these molluscs have been injured or killed by their sting. Biochemical analysis of the venom components has revealed a plethora of peptides and proteins that target a variety of receptors and ion channels. Pharmaceutical companies are now utilizing the selectivity and potency of Conus-derived peptides to develop novel medications for pain, epilepsy and other disorders.

Animals↗
PubMed2003

Non-conventional toxins from Elapid venoms.

Non-conventional toxins constitute a poorly characterized class of three-finger toxins isolated exclusively from Elapidae venoms. These toxins are monomers of 62-68 amino acid residues and contain five disulfide bridges. However, unlike alpha/kappa-neurotoxins and kappa-neurotoxins which have the fifth disulfide bridge in their middle loop (loop II), the fifth disulfide bridge in non-conventional toxins is located in loop I (N-terminus loop). Overall, non-conventional toxins share approximately 28-42% identity with other three-finger toxins including alpha-neurotoxins, alpha/kappa-neurotoxins and kappa-neurotoxins. Recent structural studies have revealed that non-conventional toxins also display the typical three-finger motif. Non-conventional toxins are typically characterized by a lower order of toxicity (LD(50) approximately 5-80 mg/kg) in contrast to prototype alpha-neurotoxins (LD(50) approximately 0.04-0.3 mg/kg) and hence they are also referred to as 'weak toxins'. Further, it is generally assumed that non-conventional toxins target muscle (alpha(2)beta gamma delta) receptors with low affinities several orders of magnitude lower than alpha-neurotoxins and alpha/kappa-neurotoxins. However, it is now known that some non-conventional toxins also antagonize neuronal alpha 7 nicotinic acetylcholine receptors. Hence, non-conventional toxins are not a functionally homogeneous group and other, yet unknown, molecular targets for this class of snake venom toxins may exist. Non-conventional toxins may therefore be a useful source of ligands with novel biological activity targeting the plethora of neuronal nicotinic receptors as well as other physiological processes.

Amino Acid Sequence↗
PubMed1998

Diversity of glutamate receptors in the mammalian retina.

The main neurotransmitters in the vertebrate retina are glutamate, GABA and glycine. Their localization in the different cell types in the retina is well known. In addition, there exists a number of neuropeptides and other neuroactive substances that are only expressed by sparse populations of neurons. In recent years, molecular biology has led to the discovery of a rapidly increasing number of neurotransmitter receptors and the apparent simplicity of neurotransmitters in the mammalian retina is contrasted by the expression of a plethora of neurotransmitter receptors and receptor subunits (not mentioning receptor isoforms). This article will concentrate on glutamate receptors with the intention of reviewing some of the recent data on glutamate receptor expression in the mammalian retina and their possible involvement in retinal function.

Animals↗