Background: Brain (B‐type) natriuretic peptide (BNP) is known to be secreted predominantly from the myocardium. Brain natriuretic peptide plasma concentrations have been shown to be markedly ...increased in patients with acute myocardial infarction; however, plasma BNP response during episodes of myocardial ischemia has not been established.
Hypothesis: This study was designed to examine plasma BNP in patients with transient myocardial ischemia induced by inflation of a percutaneous transluminal coronary angioplasty (PTCA) balloon.
Methods: Thirty consecutive patients (26 men and 4 women; mean age 61 years) who underwent PTCA, and another 49 patients (39 men and 10 women; mean age 63 years) who underwent diagnostic coronary angiography were enrolled in this study. Serum BNP concentrations were assayed in all patients.
Results: Plasma BNP was increased significantly with a peak concentration of 66.1 ± 65.2 pg/ml 24 h after PTCA. Coronary angiography did not cause plasma BNP increase (immediately before 30.4 ± 29.0 pg/ml, 24 h after 33.7 ± 30.6 pg/ml). No significant differences were present in hemodynamic parameters measured immediately before and 24 h after PTCA.
Conclusion: Plasma BNP is increased by transient myocardial ischemia induced by PTCA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Typing prion isoforms Parchi, P; Capellari, S; Chen, S. G ...
Nature (London),
03/1997, Volume:
386, Issue:
6622
Journal Article
Peer reviewed
The central event in the pathogenesis of prion diseases is the conversion of the cellular prion protein (PrP super(C)) into the pathological and protease-resistant isoform (PrP super(res)). The ...conversion produces PrP super(res) types with distinct physical and chemical characteristics, which may represent the molecular basis for prion strains. Collinge et al. extended our original observation of two types of PrP super(res) in sporadic Creutzfeldt-Jakob disease (sCJD), into iatrogenic CJD (iCJD) and the so-called new variant CJD (vCJD), which may have been acquired from bovine spongiform encephalopathy (BSE). On the basis of electrophoretic mobilities and ratios of differently glycosylated isoforms, Collinge et al. reported a total of four types of PrP super(res), but our analysis of a large series of additional cases including kuru (associated with cannibalism in the Fore tribe of New Guinea), iCJD and vCJD reveals only two patterns of electrophoretic mobility as we originally reported.
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IJS, NUK, SIK, UL, UM, UPUK
Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the ...gene encoding the prion protein (PrP). In this disorder, the vascular amyloid in tissue sections and the ≈ 7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90-147. Amyloid-laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter. They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in τ protein, and are similar to those observed in Alzheimer disease. A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We found an amber mutation in the open reading frame of the prion protein (PrP) gene. The codon 145 mutation (tyrosine to stop) was recognized on a PrP allele of a patient with Alzheimer-type ...clinical course. Pathologic examination revealed many amyloid plaques and neurofibrillary changes. However, the amyloid plaques in this patient were not composed of beta/A4 protein, but of PrP. Both wild and mutant PrP alleles were detected in the cerebral mRNA; however, only C-terminal truncated PrP was detected in the kuru plaques. We herein present evidence that only mutant PrP aggregates to make kuru plaques in the central nervous system.
We analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by the Creutzfeldt-Jakob Disease Surveillance Committee, Japan, over the past 10 ...years, since 1999. We obtained information on 1685 Japanese patients suspected as having prion diseases and judged that 1222 patients had prion diseases, consisting of definite (n = 180, 14.7%) and probable (n = 1029, 84.2%) cases, except for dura mater graft-associated Creutzfeldt–Jakob disease which also included possible cases (n = 13, 1.1%). They were classified into 922 (75.5%) with sporadic Creutzfeldt–Jakob disease, 216 (17.7%) with genetic prion diseases, 81 (6.6%) with acquired prion diseases, including 80 cases of dura mater graft-associated Creutzfeldt–Jakob disease and one case of variant Creutzfeldt–Jakob disease, and three cases of unclassified Creutzfeldt–Jakob disease (0.2%). The annual incidence rate of prion disease ranged from 0.65 in 1999 to 1.10 in 2006, with an average of 0.85, similar to European countries. Although methionine homozygosity at codon 129 polymorphism of the prion protein gene was reported to be very common (93%) in the general Japanese population, sporadic Creutzfeldt–Jakob disease in Japan was significantly associated with codon 129 homozygosity (97.5%), as reported in western countries. In sporadic Creutzfeldt–Jakob disease, MM1 type (Parchi’s classification) is the most common, as in western countries. Among atypical sporadic Creutzfeldt–Jakob disease cases, the MM2 type appeared most common, probably related to the very high proportion of methionine allele in the Japanese population. As for iatrogenic Creutzfeldt–Jakob disease, only dura mater graft-associated Creutzfeldt–Jakob disease cases were reported in Japan and, combined with the data from previous surveillance systems, the total number of dura mater graft-associated Creutzfeldt–Jakob disease was 138, comprising the majority of worldwide dura mater graft-associated Creutzfeldt–Jakob disease patients. Regarding genetic prion diseases, the most common mutation of prion protein gene was V180I (41.2%), followed by P102L (18.1%), E200K (17.1%) and M232R (15.3%), and this distribution was quite different from that in Europe. In particular, V180I and M232R were quite rare mutations worldwide. Patients with V180I or M232R mutations rarely had a family history of prion diseases, indicating that a genetic test for sporadic cases is necessary to distinguish these from sporadic Creutzfeldt–Jakob disease. In conclusion, our prospective 10-year surveillance revealed a frequent occurrence of dura mater graft-associated Creutzfeldt–Jakob disease, and unique phenotypes of sporadic Creutzfeldt–Jakob disease and genetic prion diseases related to the characteristic distribution of prion protein gene mutations and polymorphisms in Japan, compared with those in western countries.
We found 3 novel missense variants in the open reading frame of the prion protein (PrP) gene. The codon 105 point mutation (proline to leucine) was found on a codon 129 (Valine) PrP allele in 4 ...patients from 3 different Japanese families with Gerstmann-Sträussler syndrome. The codon 180 variant PrP (valine to isoleucine) was found in Creutzfeldt-Jakob disease (CJD) patients with a similar clinical course to that of codon 178 mutation. The codon 232 variant PrP (methionine to arginine) was documented in the CJD patients with typical clinical and pathological findings. These variant PrP molecules were not detected in 200 normal Japanese PrP alleles. PrP has a large repertoire of variant forms, and each primary structure of PrP corresponds to the distinct phenotype of prion diseases.
Sporadic Creutzfeldt-Jakob disease (CJD) with 129M/M, and iatrogenic and familial CJD with E200K and M232R, showed similar clinicopathologic features, a synaptic type deposition of PrPCJD, and high ...transmission frequencies to mice. Sporadic patients with 129M/V or 129V/V, and mutation cases with V180I, showed slightly different features and low or null transmission frequencies to mice. Hereditary cases with P102L, P105L, A117V, Y145stop, and insertions had different features but all demonstrated a long clinical duration and the presence of PrP plaques. The experimental transmission to mice of these mutant forms was difficult, except for one-third of the cases with P102L. CJD and related diseases, even those that are hereditary, may thus be divided into two different groups, those that are easily transmissible and those that are either difficult to transmit or nontransmissible.
To understand the significance of the accumulation of alpha B-crystallin in Rosenthal fibers within astrocytes, the expression and metabolism of alpha B-crystallin in glioma cell lines were examined ...under the conditions of heat and oxidative stress. alpha B-crystallin mRNA was increased after both stresses, and alpha B-crystallin protein moved from a detergent-soluble to a detergent-insoluble form. In addition, Western blotting of Alexander's disease brain homogenates revealed that the 27-kd heat shock protein (HSP27), which is related to alpha B-crystallin, accumulates along with alpha B-crystallin. The presence of HSP27 in Rosenthal fibers was directly demonstrated by immunohistochemistry. Our results suggest that astrocytes in Alexander's disease may be involved in an as yet unknown kind of stress reaction that causes the accumulation of alpha B-crystallin and HSP27 and results in Rosenthal fiber formation.
We developed a new immunohistochemical method by which normal tau antigenicity can be visualized in paraffin sections of formalin-fixed brain tissue. This method consists of autoclave pretreatment of ...sections immersed into distilled water (hydrated autoclaving) before incubation with anti-tau antibodies. In normal human brain, immunoreactive tau was detected in neuronal cell bodies and dendrites, axon fibers, astroglia, oligodendroglia and gray matter neuropil. In previous studies on normal tau distribution, different optimized fixations that effectively preserve tau antigenicity were used but none of these revealed all of these compartments together. Our method is therefore considered to be more sensitive for detecting normal tau immunoreactivity. In addition, hydrated autoclaving had an enhancing effect on the abnormally phosphorylated (modified) tau immunoreactivity in formalin-fixed brains. In hydrated autoclaving of sections from patients with Alzheimer's disease, neuropil threads, senile plaques, extracellular and intracellular tangles were enhanced in quantity and in staining intensity. Therefore, modified tau appears to accumulate more densely than expected from conventional immunohistochemistry. Immunoblot analysis showed that normal or modified tau immunoreactivity was totally or partially eliminated on formalin treatment and could be revisualized by hydrated autoclaving, an event presumably related to recovering of formalin-masked tau antigens through denaturation by hydrated autoclaving.
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