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  • 1
    Publication Date: 2018-06-02
    Description: Fibrillary tau aggregates in Alzheimer disease and allied neurodegenerative disorders have been visualized in vivo by PET, whereas mechanistic links between PET-detectable tau deposits and neurotoxicity remain elusive. Here, we took advantage of transgenic mouse models of tauopathies to evaluate associations between PET and postmortem measures of tau probe binding and their relation to neuronal loss. Methods: PET with a tau probe, 11 C-PBB3 (2-((1E,3E)-4-(6-( 11 C-methylamino)pyridine-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol), and volumetric MRI were performed for transgenic rTg4510 mice and nontransgenic mice. Binding of 11 C-PBB3 and its blockade by another tau binding compound, AV-1451 (-(6-fluoropyridine-3-yl)-5H-pyrido[4,3-b]indole), in homogenized brains of tauopathy patients and rTg4510 and PS19 mice were quantified, and 11 C-PBB3–positive and phosphorylated tau lesions in sectioned brains of these mice were assessed. Results: In vivo 11 C-PBB3 binding to the rTg4510 neocortex/hippocampus was increased relative to controls and correlated with local atrophy. In vitro 11 C-PBB3 binding in the neocortex/hippocampus also correlated well with in vivo radioligand binding and regional atrophy in the same individual rTg4510 mice. By contrast, in vitro 11 C-PBB3 binding was elevated in the brain stem but not hippocampus of PS19 mice, despite a pronounced loss of neurons in the hippocampus rather than brain stem. Finally, 11 C-PBB3 and AV-1451 showed similar binding properties between mouse models and tauopathy patients. Conclusion: The present findings support the distinct utilities of 11 C-PBB3 PET and MRI in rTg4510 and PS19 mice for quantitatively pursuing mechanisms connecting PET-detectable and PET-undetectable tau aggregations to neuronal death, which recapitulate 2 different modes of tau-provoked neurotoxicity.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 2
    Publication Date: 2018-09-05
    Description: Altered myocardial perfusion is a common finding in chronic Chagas cardiomyopathy (CCC), but its underlying histologic changes have not been elucidated. We investigated the occurrence of myocardial perfusion defects (MPDs) and the correlated regional changes to histology in an experimental model of CCC in hamsters. Methods: Female Syrian hamsters ( n = 34) were infected with 3.5 x 10 4 to 10 5 trypomastigote forms of Trypanosoma cruzi, Y strain, and 6–10 mo afterward underwent in vivo imaging including resting 99m Tc-sestamibi SPECT, segmental and global left ventricular function assessment using 2-dimensional echocardiography, and 18 F-FDG PET for evaluation of myocardial viability. Histologic analysis included quantification of fibrosis, inflammatory infiltration, and the diameter and density of myocardial microcirculation. Results: MPDs were present in 17 (50%) of the infected animals. Histologic analysis revealed no transmural scar in segments with an MPD, and normal or mildly reduced 18 F-FDG uptake, indicating viable myocardium. Infected animals with an MPD, in comparison to infected animals without an MPD and control animals, showed a lower left ventricular ejection fraction ( P = 0.012), a higher wall motion score index ( P = 0.004), and a higher extent of inflammatory infiltration ( P = 0.018) but a similar extent of fibrosis ( P = 0.15) and similar microvascular diameter and density ( P 〉 0.05). Segments with an MPD ( n = 65), as compared with normally perfused regions in the same animal ( n = 156), showed a higher wall motion score index ( P = 0.005) but a similar extent of inflammatory infiltration, a similar extent of fibrosis, and a similar microvascular diameter and density. Conclusion: Resting MPDs are frequent in experimental CCC and are associated with myocardial inflammation but do not designate scar tissue, corresponding to regions with metabolically viable myocardium.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 3
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two hundred and thirty five subjects from 48 German cystic fibrosis (CF) families were typed for restriction fragment length polymorphisms (RFLPs) detected by the probes pmet H, pmet D, and pJ 3.11, known to be tightly linked to the CF gene. Gene and haplotype frequencies suggest a linkage disequilibrium with the CF locus. The analysis of the predictive value of this typing in individual CF families indicates that the combined use of these probes provides a powerful diagnostic system both for carrier detection and prenatal diagnosis. In 33 out of 48 families carriers and non-carriers could be identified, and in 26 of these 33 families prenatal diagnosis could discriminate between affected and unaffected offspring.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Prenatal diagnosis of a pregnancy at risk for alpha-1-antitrypsin deficiency was performed by oligonucleotide probe analysis using M- and Z-specific oligonucleotides. The result was confirmed by the alternative approach utilizing restriction fragment length polymorphisms. Application of oligonucleotide analysis requires only fetal tissue if proteinase inhibitor types are accurately determined within the family. Our modified protocol is easy to carry out and is practicable in all laboratories where the Southern blot procedure has been established.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2307
    Keywords: Choriocarcinoma ; Hepatoid adenocarcinoma ; Small cell carcinoma ; Tubular adenocarcinoma ; Oesophagus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe an oesophageal tumour composed of choriocarcinoma, hepatoid adenocarcinoma, small cell carcinoma and tubular adenocarcinoma. The choriocarcinomatous areas and hepatoid adenocarcinomatous areas contained beta human chorionic gonadotropin-positive cells and alpha fetoprotein-positive cells, respectively. The small cell carcinomatous areas contained cells positive for serotonin or adrenocorticotrophic hormone, while the tubular adenocarcinomatous areas contained cells positive for carcinoembryonic antigen. Non-neoplastic gastric type columnar epithelium was found directly adjoing the tumour at the oral side. This tumour, with its unprecedented histology combination of tissues may hve originated in Barrett's oesophagus, although we could not confirm a history of chronic gastro-oesophageal reflux.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2099
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Summary Nonsulfur purple photosynthetic bacteria,Rhodopseudomonas spheroides cells grown aerobically in the dark were incubated with medium containing tritiated water (THO) under growth and no-growth conditions. R value defined as the ratio of specific activity (T/H) of tritium (T) incorporated into cell materials to T in medium was about 0.5 in growing cells and 0.2 in nongrowing cells regardless of THO-concentration in medium. From the fractionation of these lyophilized cells by modified Schneider method, the distribution of volatile T (i.e., exchangeable T) in cold perchloric acid (PCA)-soluble fraction, nonexchangeable T of small molecules in cold PCA- and ether-ethanol-soluble fractions and nonexchangeable T of macromolecules in hot PCA- and alkali-soluble fractions was 16 : 17 : 67 in growing cells and 38 : 24 : 38 in nongrowing cells. Moreover, the nucleic acids were extracted by phenol method from the cells incubated with THO and fractionated on methylated albumin-coated column chromatography. R value of nonexchangeable H in DNA, sRNA, and rRNA was 0.4–0.6 in growing cells and 0.06–0.13 in nongrowing cells. R value of nonexchangeable H in ribo- and deoxyribo-mononucleotides hydrolyzed by treatment with either KOH or DNase and phosphodiesterase was 0.38–0.84 in growing cells. Average R value of nonexchangeable H in nucleic acids and these mononucleotides in growing cells were similar to that of total H in the lyophilized cells. From the study of retention of T in the cells, radioactivity of T of long-lived component decreased at the biological half life of 69 h in nongrowing cells and at rate of 0.4n (n: number of cell division) in growing cells. The retention of bound T in nucleic acids of nongrowing cells was considerable, i.e., 100, 78, and 86% remaining after 16 h in DNA, sRNA, and rRNA, respectively, for 76% in the overall cells. Decrease of activity of nonexchangeable T bound to DNA in nongrowing cells was expected only the cell death.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1041
    Keywords: Temocapril ; Liver dysfunction ; angiotensin converting enzyme inhibitor ; diacid ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six subjects with normal liver function (Group 1) and 7 patients with liver dysfunction (Group 2; mean ICGR15 value 30.5 (5.2) %; range 16 to 56) received a single oral dose of 1 mg temocapril, a prodrug-type ACE inhibitor, with preferentially excreted by the biliary route. The plasma temocapril concentrations in Group 2 at 30 min and 1 h postdose were significantly higher than in Group 1, but the difference had disappeared 2 h postdosing. Although the half life of temocapril diacid in Group 2 was significantly longer than in Group 1, there was no significant difference between the two groups in AUC, Cmax or tmax. In Group 2, urinary recovery of temocapril was significantly increased, suggesting a possible delay in the bioactivation of temocapril into the diacid, but recovery of the diacid itself was not abnormal. ACE inhibitory action in Group 2 remained unchanged. Temocapril is regarded as an ACE inhibitor the disposition and efficacy of which are little affected in patients with impaired liver function.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0533
    Keywords: Glioma ; Tenascin ; Fibronectin ; Cell differentiation ; Tumor angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunohistochemical distribution of tenascin (TN), fibronectin (FN), and laminin (LN) was investigated in 56 human gliomas (8 astrocytomas, 15 anaplastic astrocytomas, and 33 glioblastomas) with regards to the histological degree of malignancy and the degree of tumor cell differentiation evaluated by the staining of glial fibrillary acidic protein (GFAP). In 8 anaplastic astrocytomas and 28 glioblastomas, TN was predominantly immunolocalized in the basement membrane zone of the proliferating tumor vessels; sections of all astrocytomas were negative for TN staining. FN was localized in the basement membrane zone of the vessels in all astrocytomas, 12 anaplastic astrocytomas, and 22 glioblastomas. In 7 anaplastic astrocytomas and 19 glioblastomas, both TN and FN were expressed to various degrees in the tumor vessels. However, most of the TN-positive vessels did not express FN, and most of the FN-positive vessels were negative for TN staining. Furthermore, in 6 anaplastic astrocytomas and 12 glioblastomas, either TN of FN, but not both, were expressed in any area on serial sections. Most of the tumor cells around TN-positive, FN-negative tumor vessels did not express GFAP. On the other hand, GFAP was present in most tumor cells around TN-negative, FN-positive vessels. LN was detected in all vascular and pial-glial basement membrane zone of the tissues examined. These findings indicate that the degree of histological malignancy and the degree of cell dedifferentiation of human gliomas correlate well with the expression of TN, but are inversely correlated with the expression of FN. We postulate that the expression of TN, but not of FN, plays a role in the promotion of angiogenesis in malignant gliomas.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 49 (1971), S. 1147-1148 
    ISSN: 1432-1440
    Keywords: ADH-bioassay ; pathogenesis of edema ; ADH-Bioassay ; ödempathogenese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Durch simultane Registrierung von Urinvolumenänderungen und elektrischer Leitfähigkeit konnte der biologische ADH-Nachweis an der hydrierten Ratte in Alkoholnarkose bei Steigerung der Empfindlichkeit verbessert werden. An gesunden Normalpersonen wurden damit durchschnittliche Plasma-ADH-Konzentrationen um 3,5 εE/ml bestimmt. Weitere Untersuchungen sind auf die Bedeutung des Hormons bei der ödempathogenese gerichtet.
    Notes: Summary By simultaneous recording of urine volume and conductivity the method of ADH determination could be improved and increased sensitivity was obtained. The mean plasma concentrations in normally hydrated healthy subjects were found to be 3.5 εU/ml. The method is used to investigate the importance of ADH in edematous states.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1440
    Keywords: ADH ; heart failure ; oedema ; ADH ; Herzinsuffizienz ; Ödem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach Entwicklung einer geeigneten biologischen Untersuchungsmethode für ADH wurden die Plasmakonzentrationen des Hormones bei Gesunden und Patienten mit kardialer Stauungsinsuffizienz untersucht. Dabei wurde festgestellt, daß bei klinisch manifester Herzinsuffizienz deutlich erhöhte Plasma-ADH-Aktivitäten gegenüber einem vergleichbaren Normalkollektiv vorliegen.
    Notes: Summary For ADH determination in man the bioassay of hydrated rats under alcohol anesthesia could essentially be improved. It was so possible to determine reproducibly the ADH concentration in normal hydrated men and patients with heart failure. The data clearly suggest that plasma ADH is elevated in the latter disease in comparison with the group of normal controls.
    Type of Medium: Electronic Resource
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