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At least 559 records · Page 31Linked to original sources
PubMedDate not supplied

TRP channels: an overview.

The TRP ("transient receptor potential") family of ion channels now comprises more than 30 cation channels, most of which are permeable for Ca2+, and some also for Mg2+. On the basis of sequence homology, the TRP family can be divided in seven main subfamilies: the TRPC ('Canonical') family, the TRPV ('Vanilloid') family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs.

Animals↗
PubMed2006

T-type calcium channels: the never ending story.

T-type, or low-voltage-activated (LVA), tiny and transient Ca2+ currents pare more and more recognised as universal players in a plethora of cell functions and are also more and more connected to several diseases. This short introduction reviews the discovery of T-type Ca2+ channels, describes its basic properties and sketches its cloning and physiological impact. Finally, an overview is given how research on T-type Ca2+ channels has developed in the last years and in which topics it is branching out, a process, which is still ongoing.

Animals↗
PubMed2006

TGF-beta receptor-binding proteins: complex interactions.

Members of the Smad protein family are fundamental downstream mediators of TGF-beta signals. However, the basic, linear Smad signaling pathway is unlikely to be the sole contributor to the plethora of cell type-specific TGF-beta responses. Investigators have identified a number of molecules that interact with the TGF-beta receptors (TbetaRs) and may explain, at least in part, the tight regulation of TGF-beta effects. Understanding these TbetaR-interacting molecules is thus a matter of great potential significance for elucidating TGF-beta-family signal transduction. The present article reviews our current understanding of the roles and mechanisms of action of this relatively understudied group of molecules.

Animals↗
PubMed2004

Antiviral therapy: nucleotide and nucleoside analogs.

For the management of HBV infection, an increasing number of nucleotide and nucleoside analogs are active against wild-type HBV and some against HBV with YMDD and other compensatory mutations. Table 2 depicts the IC50 and susceptibilities of HBV to various antiviral agents. The dichotomy between in vitro and in vivo susceptibilities to YMDD mutants is due to a change in IC50 between wild-type and mutant virus. Thus a drug may have less activity in vitro but at doses used in vivo show activity against YMDD and other compensatory mutations. Some HBV drugs share activity against HIV, which may be useful in the co-infected patient. Other nucleoside analogs are in various stages of development, including MCC-478 and DAPD. In the future, clinicians will have a plethora of reagents to chose from, and combination therapies may be invoked.

Antiviral Agents↗
PubMed2004

Medical errors: overcoming the challenges.

The issue of medical errors has received substantial attention in recent years. The Institute of Medicine (IOM) report released in 1999 has several implications for health care systems in all disciplines of medicine. Notwithstanding the plethora of available information on the subject, little, by way of substantive action, is done toward medical error reduction. A principal reason for this may be the stigma associated with medical errors. An educational program with a practical, informed, and longitudinal approach offers realistic solutions toward this end. Effective reporting systems need to be developed as a medium of learning from the errors and modifying behaviors appropriately. The presence of a strong leadership supported by organizational commitment is essential in driving these changes. A national, provincial or territorial quality care council dedicated solely for the purpose of enhancing patient safety and medical error reduction may be formed to oversee these efforts. The bioethical and emotional components associated with medical errors also deserve attention and focus.

Health Education↗
PubMedDate not supplied

Cushing's syndrome.

Cushing's syndrome results from prolonged exposure to excess glucocorticoids. Patients with Cushing's syndrome may develop multiple metabolic problems including obesity, hyperglycemia, hypertension, depression, low bone mass, muscle atrophy, and hypogonadism. Cutaneous manifestations of hypercortisolism include skin atrophy, excessive bruising, purple striations, poor wound healing, facial plethora, vellous hypertrichosis and hirsutism. Diagnostic tests used to screen for Cushing's syndrome include 24-hour urine cortisol, the 1 mg dexamethasone suppresion test, and late night salivary cortisol. A normal screening test excludes the diagnosis of Cushing's. Patients with an abnormal screening test should be referred to an endocrinologist for complete evaluation of the pituitary-adrenal axis.

Cushing Syndrome↗
PubMed2005

Distinguishing features of developing natural killer cells.

Although NK cells were initially described as lymphocytes that lacked the characteristic markers of B and T cells, we now appreciate the plethora of activating and inhibitory receptors that define the NK cell surface phenotype. Recent studies have provided new insights into the molecular mechanisms that drive NK cell development, control the NK cell receptor repertoire and the cytokines that define the NK cell niche. These findings form the basis for an updated model of NK cell differentiation.

Animals↗
PubMed2005

Systems biology of neutrophil differentiation and immune response.

Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function in a context-dependent manner.

Animals↗
PubMed2006

Somatic hypermutation: subverted DNA repair.

Somatic hypermutation generates high-affinity antibodies of different isotypes that efficiently protect us against a plethora of pathogens. Recent analyses of the types of mutations produced in gene-deficient mice have indicated how DNA repair proteins are drawn into the pathway. Activation-induced cytosine deaminase begins the process by deaminating cytosine to uracil in DNA. The uracils are then recognized by the base excision repair protein uracil DNA glycosylase and by the mismatch repair proteins MutS homologue 2 and MutS homologue 6. Instead of repairing the uracils, these proteins attract low fidelity DNA polymerases, which synthesize nucleotide substitutions at an unprecedented level.

Animals↗
PubMed2005

Orthobiologics: a survey of materials and techniques.

The modern study of the regenerative capabilities of skeletal tissues began in 1964, when Marshall Urist discovered that bone devoid of inorganic content and dried into a powder could be implanted into the muscle of a rabbit with resultant ectopic bone formation. Use of this technology is now commonplace, and a plethora of orthobiologic materials are available to the foot and ankle surgeon. The science has even become advanced to the point that custom bone replacements can be fabricated in vitro. This points toward an exciting future for the use of this technology by foot and ankle surgeons.

Animals↗
PubMedDate not supplied

Microarray analysis using bioinformatics analysis audit trails (BAATs).

Bioinformatics analysis plays an integrative role in genomics and functional genomics. The ability to conduct quality managed, hypothesis-driven bioinformatics analysis with the plethora of data available is mandatory. Biological interpretation of this data is dependent on versions of databases, programs and the parameters used. Thus, tracking and auditing the analyses process is important. This paper outlines what we term Bioinformatics Analysis Audit Trails (BAATs) and describes YABI, a bioinformatics environment that implements BAATs. YABI can incorporate most bioinformatics tools within the same environment, making it a valuable resource.

Computational Biology↗
PubMed2005

The lac repressor.

Few proteins have had such a strong impact on a field as the lac repressor has had in Molecular Biology. Over 40 years ago, Jacob and Monod [Genetic regulatory mechanisms in the synthesis of proteins, J. Mol. Biol. 3 (1961) 318] proposed a model for gene regulation, which survives essentially unchanged in contemporary textbooks. It is a cogent depiction of how a set of 'structural' genes may be coordinately transcribed in response to environmental conditions and regulates metabolic events in the cell. In bacteria, the genes required for lactose utilization are negatively regulated when a repressor molecule binds to an upstream cis activated operator. The repressor and its operator together form a genetic switch, the lac operon. The switch functions when inducer molecules alter the conformation of the repressor in a specific manner. In the presence of a particular metabolite, the repressor undergoes a conformational change that reduces its affinity for the operator. The structures of the lac repressor and its complexes with operator DNA and effector molecules have provided a physical platform for visualizing at the molecular level the different conformations the repressor and the molecular basis for the switch. The structures of lac repressor, bound to its operator and inducer, have also been invaluable for interpreting a plethora of biochemical and genetic data.

Allosteric Site↗
PubMed2003

Calcium signalling: the ups and downs of protein kinase C.

Oscillations in intracellular calcium levels control a plethora of physiological processes, but how they are decoded by a cell remains unclear. In a recent study, advances in FRET technology have been used to describe how calcium oscillations are decoded through phase-locked oscillations in substrate phosphorylation catalysed by protein kinase C.

Animals↗
PubMed2004

Bidirectional transport along microtubules.

Active transport by microtubule motors has a plethora of crucial roles in eukaryotic cells. Organelles often move bidirectionally, employing both plus-end and minus-end directed motors. Bidirectional motion is widespread and may allow dynamic regulation, error correction and the establishment of polarized organelle distributions. Emerging evidence suggests that motors for both directions are simultaneously present on cellular 'cargo', but that their activity is coordinated so that when plus-end motors are active, minus-end motors are not, and vice versa. Both the dynein cofactor dynactin and the Klarsicht (Klar) protein appear to be important for such coordination. The direction of net transport depends on the balance between plus-end directed and minus-end directed motion. In several model systems, factors crucial for setting this balance have now been identified, setting the stage for a molecular dissection of the underlying regulatory mechanisms. These analyses will likely provide insight into motor cooperation in general.

Biological Transport, Active↗
PubMed2004

Anesthesia of the critically ill equine patient.

There is a plethora of information regarding anesthetic management of horses; however, controlled studies of the critically ill equine patient are few. These patients should be managed like any equine anesthetic candidate but much more stringently:I. Preoperative evaluation and appropriate therapy may represent the difference between life and death during the intraoperative and recovery periods. 2. The anesthetic induction and maintenance protocol should be based on the individual situation of the veterinary facility and personnel("comfort zone"). 3. Appropriate monitoring and intraoperative supportive measures are essential. 4. The anesthetic period is a significant perturbation to homeostasis. Even if the horse seems to have done well (ie, as indicated by the cardiopulmonary values), a problem-free anesthetic period does not guarantee a successful recovery, and close monitoring should continue until the horse is ambulatory. 5. Critically ill patients are often in a negative energy balance. Supportive measures to ensure an adequate caloric intake, such as enteral or parenteral nutrition, facilitate healing and return of homeostasis.

Anesthesia↗
PubMed2006

Topical and systemic medications for wounds.

There are a plethora of topical and systemic medications available to the veterinary practitioner today that aid the wound healing process. Some of these help to maintain a moist environment. Others increase growth factors, provide local energy sources, control infection, provide for debridement, increase wound blood flow and temperature, or reduce wound edema. Modern wound care requires that the proper products(s)be used, depending on the condition of the wound and the phase of wound healing. This article discusses various wound care products and provides guidelines on their use.

Administration, Topical↗
PubMed2006

Data reduction and representation in drug discovery.

Pre-clinical drug discovery relies increasingly on huge volumes of inter-related multivariate data. To make sense of these data and enable quality decision-making based on this plethora of information they must be presented in an interpretable form. Reducing the dimensionality of the data often leaves a data set that is too complex to interpret readily, so intuitive visualization methods are needed. Bioinformatics has provided much of the impetus for visualizing complex data, the cheminformatics community has been aggressive with the data-reduction problem. The increasing appreciation of the inter-related multifactorial nature of pre-clinical drug discovery makes visualization a burgeoning and active field that spans biosciences, mathematics and visual psychology.

Computational Biology↗
PubMed2006

Spatial organisation of AKAP18 and PDE4 isoforms in renal collecting duct principal cells.

A plethora of stimuli including hormones and neurotransmitters mediate a rise of the cellular level of cAMP and thereby activation of protein kinase A (PKA). PKA phosphorylates and thereby modulates the activity of a wide range of cellular targets. It is now appreciated that different stimuli induce the activation of PKA at specific sites where the kinase phosphorylates particular substrates in close proximity. The tethering of PKA to cellular compartments is facilitated by A kinase-anchoring proteins (AKAPs). The incorporation of phosphodiesterases (PDEs) into AKAP-based signalling complexes provides gradients of cAMP that regulate PKA activity locally. An example for a process depending on compartmentalised cAMP/PKA signalling is the arginine-vasopressin (AVP)-mediated water reabsorption in renal collecting duct principal cells. Upon activation through AVP, PKA phosphorylates the water channel aquaporin-2 (AQP-2) located on intracellular vesicles. The phosphorylation triggers the redistribution of AQP2 to the plasma membrane. AKAP-anchored PKA has been shown to be involved in AQP2 shuttling. Here, AKAP18 isoforms and members of the PDE4 family of PDEs are shown to be differentially localised in renal principal cells.

3',5'-Cyclic-AMP Phosphodiesterases↗