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  • Articles  (347)
  • Blackwell Publishing Ltd  (347)
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  • Articles  (347)
  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 53 (1989), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A novel serine/threonine-specific protein kinase was isolated from the microvessels of porcine brains- The molecular mass of the protein is 80,000 daltons, as judged by gel electrophoresis under denaturing conditions, or J 22,000 daltons. on high-resolution gel permeation chromatography in the native state. The activity of this enzyme is stimulated by various histones or polyamines, like spermine or spermidine, but not by any of the common second messengers. The amino-terminal sequence data show no homologies to any of the published kinases, but rather to a heat-shock protein of unknown function.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Cardiovascular drug reviews 22 (2004), S. 0 
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of glaucoma therapy is to preserve vision by reducing intraocular pressure (IOP). Following recent National Eye Institute sponsored studies, it is becoming increasingly apparent that every mmHg of extra IOP lowering counts.Bimatoprost is the newest and most effective addition to the physician's armamentarium of ocular hypotensive drugs. Direct clinical comparisons have demonstrated that it is more efficacious than the prostaglandin (PG) FP receptor agonist prodrugs, latanoprost and travoprost, as well as a β-adrenoceptor antagonist, timolol, alone or in fixed combination with the carbonic anhydrase inhibitor, dorzolamide. Moreover, patients that are refractory to latanoprost therapy may be successfully treated with bimatoprost. Such evidence provides support, at the clinical level, for the contention that bimatoprost is pharmacologically distinct from PG FP receptor agonist prodrugs.Bimatoprost is a structural analog of PGF2α-ethanolamide (prostamide F2α), which is formed from the endocannabinoid anandamide by a biosynthetic pathway involving cyclooxygenase-2 (COX-2). Their pharmacology is remarkably similar, such that bimatoprost may be regarded as a prostamide mimetic. The target receptor for bimatoprost and the prostamides appears unique and unrelated to PG- and endocannabinoid-sensitive receptors. Extensive ocular distribution/metabolism studies in non-human primates demonstrate that bimatoprost is not a prodrug, it remains essentially intact. Its profound ocular hypotensive effects may, therefore, be attributed to its prostamide-mimetic properties.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    The @breast journal 4 (1998), S. 0 
    ISSN: 1524-4741
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: abstract Purpose. The role of frozen section analysis during breast conversation surgery is undefined. Assessment of margins using eprmanent section evaluation is the standard method of ensuring complete tumor excision. If the margin is positive, however, surgical re-excision is necessary to reduce the likelihood of subsequent local recurrence. Therefore, biopsy of the surgical cavity with immediate pathological evaluation during lumpectomy was performed to evaluate the effect on local recurrence, the number of re-excisions, and cosmesis. Patients and Methods. One hundred sixty patients underwent attempted lumpectomy with frozen section margin determination. One hundred forty patients were available for long-term follow-up (mean = 57 months, median = 46 months). All patients underwent attempted breast conservation surgery, which consisted of tumorectomy with excision of a greater than 1-cm rim of grossly normal tissue. Tumor margins were obtained by intraoperative biopsy with frozen section analysis of the lumpectomy cavity walls. Results. In 21 patients (15%), frozen section analyses (FSA) revealed positive margins, resulting in immediate re-excision. In seven of these patients (%), margins were persistetly positive, and these patients therefore underwent mastectomy. Fourteen patients were successfully re-excised to a negative margin. The sensitivity and specificity of FSA were 91% and 100%, respectively. Five percent of patients definitively managed by lumpectomy with FSA of margins recurred locally. The mean cosmesis score after radiotherapy was 7.0 out of a possible 10, correlating with a good to excellent result. Discussion. The accuracy of FSA, low recurrence rate, avoidance of reoperation, and good cosmesis indicate that intraoperative frozen section analysis should be adopted as a safe and effective method of margin analysis during breast conservation surgery.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1527-3466
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of prosthodontics 11 (2002), S. 0 
    ISSN: 1532-849X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Chemicals that are active at the benzodiazepine receptor (endozepines) are naturally present in the CNS. These substances are present in tissue from humans and animals and in plants and fungi. Using selective extraction protocols, HPLC purification, receptor binding displacement studies, and selective anti-benzodiazepine antibodies, we have identified six or seven peaks of endozepines in rat and human brain. All material could competitively displace [3H]flunitrazepam binding to cerebellar benzodiazepine binding sites. Two peaks also competitively displaced Ro 5-4864 binding to the mitochondrial benzodiazepine binding site. Total amounts of brain endozepines were estimated to be present in potentially physiological concentrations, based on their ability to displace [3H]flunitrazepam binding. Although endozepine peaks 1 and 2 had HPLC retention profiles similar to those of nordiazepam and diazepam, respectively, gas chromatography-mass spectrometry as well as high-performance TLC revealed biologically insignificant amounts of diazepam (〈 0.02 pg/g) and nordiazepam (〈0.02 pg/g) in the purified material. Electrophysiologically, some purified endozepines positively modulated γ-aminobutyric acid (GABA) action on Cl− conductance, monitored in patch-clamped cultured cortical neurons or in mammalian cells transfected with cDNA encoding various GABAA receptor subunits. These studies demonstrate that mammalian brains contain endozepines that could serve as potent endogenous positive allosteric modulators of GABAA receptors.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 56 (1991), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The rabbit cerebellum has been shown to contain significant quantities of opioid receptors consisting of both γ- and k-subtypes. To determine the nature of the endogenous opioid ligands in this tissue, extracts from rabbit cerebellum were separated by various chromatography techniques and fractions were assayed initially for opioid peptides with a radioimmunoassay capable of detecting all peptides with an amino-terminal Tyr-Gly-Gly-Phe sequence. This sequence is common to all mammalian opioid peptides and is critical for recognition by all known opioid receptors. Each of the three immunoreactive opioid peptide peaks detected was purified to homogeneity and subjected to amino acid composition and sequence analysis. One peak was analyzed further by mass spectrometry. This identified the major opioid peptides in the cerebellum as [Met5]enkephalin, [Leu5]enkephalin, and heptapeptide [Met5]enkephalyl-Arg6-Phe7. The comprehensiveness of this initial detection scheme in identifying biologically active opioid peptides was substantiated through subsequent analysis. Using specific radioimmunoassays for representative opioid peptides of the three opioid systems currently known, no other peptides of either the proenkephalin, proopiomelanocortin, or prodynorphin series were detected in any appreciable amounts. Collectively, these results are consistent with the position that rabbit cerebellar opioids are derived from proenkephalin. However, given that no appreciable quantities of either [Met5]enkephalyl-Arg6-Arg7-Val8-NH2 (metorphamide) or [Met5]enkephalyl-Arg6-Gly7-Leu8 were detected suggests that rabbit proenkephalin may have a slightly altered sequence and/or is differentially processed relative to other mammalian species studied.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A1 adenosine receptors were labeled in rat brain sections with the antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and visualized at the light microscopic level using autoradiography. The specific binding of [3H]DPCPX to the sections showed the pharmacological characteristics of A1 adenosine receptors and was accompanied by very low levels of nonspecific binding. Whereas GTP had no significant effect on [3H]DPCPX binding to rat brain membranes, the addition of 100 μM GTP increased the apparent affinity of [3H]DPCPX to tissue sections fivefold (from 1.83 to 0.35 nM), enhancing it to the affinity measured in membranes. However, GTP altered neither the binding capacity nor the distribution of binding sites in tissue sections. It is suggested that a competitive antagonism with endogenous adenosine explains the lower affinity of [3H]DPCPX in the absence of GTP. The autoradiographic pattern of [3H]DPCPX binding was characteristic for A1 adenosine receptors. Distinct labeling of the different layers of the cerebellar cortex was shown by photomicrographs generated with the coverslip technique. In addition, several fiber tracts were found to be labeled. The high selectivity for A1 adenosine receptors and low nonspecific binding of [3H]DPCPX, the ability to produce high-resolution autoradiograms, together with the fact that the effects of endogenous adenosine can be eliminated by the addition of GTP make [3H]DPCPX a very useful tool in the autoradiographic study of A1 adenosine receptors.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 61 (1993), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Two heme oxygenase (HO) isozymes—HO-1, which is a heat shock protein (HSP32), and HO-2—catalyze the isomer-specific production of biliverdin IXα and carbon monoxide. The latter has the potential of functioning as a neurotransmitter, whereas the reduced form of biliverdin, bilirubin, has potent antioxidant activity. Formation of bilirubin is catalyzed by biliverdin reductase (BVR). The reductase is a unique enzyme in being dual pyridine nucleotide and dual pH dependent. Here, we show that the reductase is resistant to thermal stress at both the protein and message level. We further demonstrate that the reductase is coexpressed in cells that display HO-1 and/or HO-2 under normal conditions, as well as in regions and cell types that have the potential to express heat shock-inducible HO-1 protein. Exposure of male rats to 42°C for 20 min did not decrease brain BVR activity, but caused a slight increase in NADPH-and NADH-dependent activities at 1 and 6 h following hyperthermia. High levels of the ∼ 1.5-kb BVR mRNA were detected in control brain; it too displayed thermal tolerance. Similarly, the pattern of multiplicity of net charge variants of the enzyme purified from brain of heat-shocked rats did not differ from the control pattern. Immunochemical localization of BVR protein in normal brain correlated well with the presence of HO-1 and/or HO-2 throughout the forebrain, diencephalon, cerebellum, and brainstem regions. There were select neuronal and nonneuronal cells in the substantia nigra and cerebellum that did express the reductase under normal conditions, wherein no HO isozymes could be detected. The same population, however, responded to heat shock by an intense increase in the level of HO-1. We postulate that the constitutive presence of the reductase in this cell population and the overall thermal stability of the enzyme represent a safeguard mechanism in the brain for the prompt conversion of biliverdin to bilirubin under conditions when oxidation of the heme moiety of denatured hemoproteins by HO-1 is accelerated.
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  • 10
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti-benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti-benzodiazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained ∼ 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased ∼ 10-fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy.
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