Abnormal Form (abnormal + form)

Distribution by Scientific Domains


Selected Abstracts


Hyperefficient PrPSc amplification of mouse-adapted BSE and scrapie strain by protein misfolding cyclic amplification technique

FEBS JOURNAL, Issue 10 2009
Aiko Fujihara
Abnormal forms of prion protein (PrPSc) accumulate via structural conversion of normal PrP (PrPC) in the progression of transmissible spongiform encephalopathy. Under cell-free conditions, the process can be efficiently replicated using in vitro PrPSc amplification methods, including protein misfolding cyclic amplification. These methods enable ultrasensitive detection of PrPSc; however, there remain difficulties in utilizing them in practice. For example, to date, several rounds of protein misfolding cyclic amplification have been necessary to reach maximal sensitivity, which not only take several weeks, but also result in an increased risk of contamination. In this study, we sought to further promote the rate of PrPSc amplification in the protein misfolding cyclic amplification technique using mouse transmissible spongiform encephalopathy models infected with either mouse-adapted bovine spongiform encephalopathy or mouse-adapted scrapie, Chandler strain. Here, we demonstrate that appropriate regulation of sonication dramatically accelerates PrPSc amplification in both strains. In fact, we reached maximum sensitivity, allowing the ultrasensitive detection of < 1 LD50 of PrPSc in the diluted brain homogenates, after only one or two reaction rounds, and in addition, we detected PrPSc in the plasma of mouse-adapted bovine spongiform encephalopathy-infected mice. We believe that these results will advance the establishment of a fast, ultrasensitive diagnostic test for transmissible spongiform encephalopathies. [source]


Synthesis and structural characterization of a mimetic membrane-anchored prion protein

FEBS JOURNAL, Issue 6 2006
Matthew R. Hicks
During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP,GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP,GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP. [source]


Prion diseases: contribution of high-resolution immunomorphology

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2001
J-G. Fournier
Abstract The transmisible spongiform encephalopathies or prion diseases are fatal neurological diseases that occur in animals and humans. They are characterized by the accumulation in the cerebral tissue of the abnormal form of prion protein (PrPsc) produced by a post-translational event involving conformational change of its normal cellular counterpart (PrPc). In this short review, we present some results on the biology of prion proteins which have benefited from morphological approaches combining the electron microscopy techniques and the immunodetection methods. We discuss data concerning in particular the physiological function of the normal cellular prion prion (PrPc) which have allowed to open up new vistas on prion diseases, the biogenesis of amyloid plaque and the cellular site involved in the prion protein conversion process. [source]


Strain-Associated Variations in Abnormal PrP Trafficking of Sheep Scrapie

BRAIN PATHOLOGY, Issue 1 2009
FRC Path, MRCVS, Martin Jeffrey BVMS DVM Dip ECVP
Abstract Prion diseases are associated with the accumulation of an abnormal form of the host-coded prion protein (PrP). It is postulated that different tertiary or quaternary structures of infectious PrP provide the information necessary to code for strain properties. We show here that different light microscopic types of abnormal PrP (PrPd) accumulation found in each of 10 sheep scrapie cases correspond ultrastructurally with abnormal endocytosis, increased endo-lysosomes, microfolding of plasma membranes, extracellular PrPd release and intercellular PrPd transfer of neurons and/or glia. The same accumulation patterns of PrPd and associated subcellular lesions were present in each of two scrapie strains present, but they were present in different proportions. The observations suggest that different trafficking pathways of PrPd are influenced by strain and cell type and that a single prion strain causes several PrPd,protein interactions at the cell membrane. These results imply that strains may contain or result in production of multiple isoforms of PrPd. [source]


Immunohistochemistry for the Prion Protein: Comparison of Different Monoclonal Antibodies in Human Prion Disease Subtypes

BRAIN PATHOLOGY, Issue 1 2002
Gábor G. Kovács MD
Demonstration of the abnormal form of the prion protein (PrP) in the brain confirms the diagnosis of human prion disease (PrD). Using immunohistochemistry, we have compared ten monoclonal antibodies in PrD subtypes including sporadic and variant Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Alzheimer's disease (AD), and control brains. CJD subgroups were determined using Western blot analysis for the protease-resistant PrP type in combination with sequencing to determine the genotype at the methionine/valine polymorphism at codon 129 of the prion protein gene. None of the antibodies labeled given subgroups exclusively, but the intensity of immunoreactivity varied among morphologically distinct types of deposit. Fine granular or synaptic PrP deposits stained weakly or not at all with antibodies against the N-terminus of PrP, and were visible in one case only with 12F10 and SAF54. Coarser and plaque type deposits were immunolabeled with all antibodies. The immunostaining patterns appear characteristic for the disease subgroups. Labeling of certain neurons in all cases irrespective of disease, and staining at the periphery and/or throughout the senile plaques of AD patients were also noted. Antibodies such as 6H4 and 12F10 failed to give this type of labeling and are therefore less likely to recognise non-pathological PrP material in immunohistochemistry. [source]


Unusual insertion of the coracobrachialis muscle to the brachial fascia associated with high division of brachial artery

CLINICAL ANATOMY, Issue 8 2004
Bappaditya Ray
Abstract Anatomical variations of the coracobrachialis muscle (CBM) are common. We detected an abnormal form of the CBM of the left arm during human cadaver dissection. The CBM originated from the tip of the coracoid process of the scapula and divided into muscular and musculo-aponeurotic bellies. The muscular belly inserted into the middle of the anteromedial surface of the humerus, which is the normal anatomic insertion point of the CBM. The musculo-aponeurotic belly inserted into the medial intermuscular septum as well as the brachial fascia, creating a tunnel for the passage of the brachial artery. Inside the tunnel, the brachial artery bifurcated into the radial and ulnar arteries. No abnormality of the CBM, the brachial artery, or the median nerve was detected in the contralateral arm. The phylogenic, ontogenic, functional, and clinical importance of this variant muscle is described. Knowledge of such variations is of considerable importance during invasive and non-invasive investigative procedures or orthopedic, reconstructive, or surgical procedures. Clin. Anat. 17:672,676, 2004. © 2004 Wiley-Liss, Inc. [source]


Two bellies of the coracobrachialis muscle associated with a third head of the biceps brachii muscle

CLINICAL ANATOMY, Issue 5 2001
Mostafa M. El-Naggar
Abstract Reports that describe the abnormalities and complexities of the anatomy of the arm are important with regard to surgical approaches. This case study reports a combined abnormal form of the coracobrachialis and biceps brachii muscles of the left arm of an adult male cadaver that was detected during the educational gross anatomy dissections of embalmed cadavers. The coracobrachialis muscle demonstrated two bellies which formed shortly inferior to its origin from the coracoid process of the scapula. One belly inserted into the middle of the antero-medial surface of the humerus, whereas the other belly inserted into the medial head of the triceps brachii muscle. The musculocutaneous nerve passed between the two bellies, giving a separate branch to each. We suggest that the two bellies of the coracobrachialis muscle may represent the incompletely fused short heads of the ancestral muscle. The biceps brachii muscle showed a third head, which originated mainly from the antero-medial surface of the humerus and partially from an aponeurosis belonging to the medial head of the triceps brachii muscle. These observations were confined to the left upper limb and were not accompanied by any other abnormality. Clin. Anat. 5:379,382, 2001. © 2001 Wiley-Liss, Inc. [source]


Classical sheep transmissible spongiform encephalopathies: pathogenesis, pathological phenotypes and clinical disease

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2007
M. Jeffrey
Scrapie is a prion disease or transmissible spongiform encephalopathy (TSE) of sheep, goats and moufflon. As with its human counterparts, pathology consists of vacuolation, gliosis and accumulations of abnormal forms of a host prion protein (PrPd) in the brain of affected individuals. Immunohistochemical methods can be used to identify both the intracellular truncation sites of PrPd in different cell types (PrPd epitope mapping) and the different morphological patterns of accumulation (PrPd profiling). Differences in the inferred truncation sites of PrPd are found for different strains of sheep TSEs and for different infected cell types within individual strains. Immunochemical methods of characterizing strains broadly correspond to PrPd mapping discriminatory results, but distinct PrPd profiles, which provide strain- and source-specific information on both the cell types which sustain infection (cellular tropisms) and the cellular processing of PrPd, have no immunoblotting counterparts. The cause of neurological dysfunction in human is commonly considered to be neuronal loss secondary to a direct or indirect effect of the accumulation of PrPd. However, in sheep scrapie there is no significant neuronal loss, and relationships between different magnitudes, topographical and cytological forms of PrPd accumulation and clinical signs are not evident. PrPd accumulation also occurs in lymphoid tissues, for which there is indirect evidence of a pathological effect, in the peripheral nervous system and in other tissues. It is generally assumed that neuroinvasion results from infection of the enteric nervous system neurones subsequent to amplification of infectivity in lymphoid tissues and later spread via sympathetic and parasympathetic pathways. The evidence for this is, however, circumstantial. Accumulation of PrPd and presence of infectivity in tissues other than the nervous and lymphoreticular systems gives insights on the ways of transmission of infection and on food safety. [source]


Heme oxygenase enzyme activity in seminal plasma of oligoasthenoteratozoospermic males with varicocele

ANDROLOGIA, Issue 4 2010
M. T. Abdel Aziz
Summary This work aimed to assess seminal plasma heme oxygenase (HO) enzyme activity in oligoasthenoteratozoospermia (OAT) males with varicocele. Ninety-three men were divided according to their sperm count and clinical examination into: healthy fertile controls (n = 34), OAT without varicocele (n = 37) and OAT associated with varicocele (n = 22). They were subjected to semen analysis and estimation of seminal plasma HO enzyme activity in the form of bilirubin concentration. Seminal plasma HO enzyme activity decreased significantly in OAT cases compared with controls. Seminal plasma HO in OAT cases associated with varicocele decreased significantly compared with OAT cases without varicocele and healthy controls (mean ± SD; 109.2 ± 29.5, 283.6 ± 88.4, 669.5 ± 236.1 nMol bilirubin/mg ptn/min, P < 0.001). There was positive correlation between seminal plasma HO enzyme activity and sperm concentration, per cent of motile spermatozoa, number of motile spermatozoas ml,1 and significant negative correlation with sperm abnormal forms per cent. It is concluded that varicocele has a negative impact on seminal HO enzyme activity. Therefore, improved seminal picture after correcting varicocele repair might be related, in part, to improved HO action(s). [source]


Effect of smoking on seminal plasma ascorbic acid in infertile and fertile males

ANDROLOGIA, Issue 6 2006
T. Mostafa
Summary This work aimed to assess the relationship of seminal ascorbic acid levels with smoking in infertile males. One hundred and seventy men were divided into four groups: nonobstructive azoospermia [NOA: smokers (n = 20), nonsmokers (n = 20)]; oligoasthenozoospermia [smokers (n = 30), nonsmokers (n = 20)]; asthenozoospermia [smokers (n = 20), nonsmokers (n = 20)] and normozoospermic fertile men [smokers (n = 20), nonsmokers (n = 20)]. The patients underwent medical history, clinical examination, conventional semen analysis and estimation of ascorbic acid in the seminal plasma calorimetrically. There was a significant decrease in the mean seminal plasma ascorbic acid levels in smokers versus nonsmokers in all groups (mean ± SD; 6.03 ± 2.18 versus 6.62 ± 1.29, 7.81 ± 1.98 versus 9.44 ± 2.15, 8.09 ± 1.98 versus 9.95 ± 2.03, 11.32 ± 2.15 versus 12.98 ± 12.19 mg dl,1 respectively). Fertile subjects, smokers or not, demonstrated significant higher seminal ascorbic acid levels than any infertile group. Seminal plasma ascorbic acid in smokers and nonsmokers was correlated significantly with sperm concentration (r = 0.59, 0.60, P < 0.001), sperm motility (r = 0.65, 0.55, P < 0.001) and negatively with sperm abnormal forms per cent (r = ,0.53, ,0.50, P < 0.001). Nonsignificant correlations were elicited with semen volume (r = 0.2, 0.09) or liquefaction time (r = 0.03, 0.06). It is concluded that seminal plasma ascorbic acid decreased significantly in smokers and infertile men versus nonsmokers and fertile men, and is significantly correlated with the main sperm parameters: count, motility and normal morphology. Also, cigarette smoking is associated with reduced semen main parameters that could worsen the male fertilizing potential, especially in borderline cases. [source]