Expression of high molecular weight tau in the central and peripheral nervous systems

1993 ◽  
Vol 105 (3) ◽  
pp. 729-737
Author(s):  
I.S. Georgieff ◽  
R.K. Liem ◽  
D. Couchie ◽  
C. Mavilia ◽  
J. Nunez ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Molecular Weight ◽  
Nervous System ◽  
High Molecular Weight ◽  
Tumor Cells ◽  
Apparent Molecular Weight ◽  
In Vitro Transcription ◽  
The Central Nervous System ◽  
Immunohistochemical Studies

Using a novel PCR approach, we have cloned a cDNA encoding the entire high molecular weight tau molecule from rat dorsal root ganglia. The resulting 2080 bp cDNA differs from low molecular weight rat brain tau by the insertion of a novel 762 bp region (exon 4a) between exons 4 and 5. This cDNA clone is identical in sequence with a high molecular weight tau (HMW) cDNA from rat PC12 tumor cells and is closely related to a HMW tau cDNA from mouse N115 tumor cells. In vitro transcription/translation produces a protein that migrates on SDS-PAGE with the same apparent molecular weight as HMW tau purified from rat sciatic nerve. The HMW tau protein is generated from an 8 kb mRNA, which can be detected by northern blots in peripheral ganglia, but not in brain. A more sensitive assay using PCR and Southern blot analysis demonstrates the presence of exon 4a in spinal cord and in retina. In combination with immunohistochemical studies of spinal cord, these data suggest that HMW tau, though primarily in the peripheral nervous system, is also expressed in limited areas of the central nervous system, although its presence cannot be detected in the cerebral cortices.

scholarly journals The cercarial glycocalyx of Schistosoma mansoni.

1985 ◽  
Vol 100 (5) ◽  
pp. 1423-1434 ◽  
Author(s):  
J C Samuelson ◽  
J P Caulfield
Keyword(s):  
Electron Microscopy ◽  
Molecular Weight ◽  
Schistosoma Mansoni ◽  
High Molecular Weight ◽  
Membrane Surface ◽  
Periodate Oxidation ◽  
Apparent Molecular Weight ◽  
Ruthenium Red ◽  
Unit Membrane

Cercariae, the freshwater stage of Schistosoma mansoni infectious to man, are covered by a single unit membrane and an immunogenic glycocalyx. When cercariae penetrate the host skin, they transform to schistosomula by shedding tails, secreting mucous and enzymes, and forming microvilli over their surface. Here the loss of the glycocalyx from cercariae transforming in vitro was studied morphologically and biochemically. By scanning electron microscopy, the glycocalyx was a dense mesh composed of 15-30 nm fibrils that obscured spines on the cercarial surface. The glycocalyx was absent on organisms fixed without osmium and was partially lost when parasites aggregated in their own secretions before fixation. By transmission electron microscopy, a 1-2 microns thick mesh of 8-15-nm fibrils was seen on parasites incubated with anti-schistosomal antibodies or fixed in aldehydes containing tannic acid or ruthenium red. Cercariae transformed to schistosomula when tails were removed mechanically and parasites were incubated in saline. Within 5 min of transformation, organisms synchronously formed microvilli which elongated to 3-5 microns by 20 min and then were shed. However, considerable fibrillar material remained adherent to the double unit membrane surface of schistosomula. For biochemical labeling, parasites were treated with eserine sulfate, which blocked cercarial swimming, secretion, infectivity, and transformation to schistosomula. Material labeled by periodate oxidation and NaB3H4 was on the surface as shown by autoradiography and had an apparent molecular weight of greater than 10(6) by chromatography. Periodate-NaB3H4 glycocalyx had an isoelectric point of 5.0 +/- 0.4 and was precipitable with anti-schistosomal antibodies. More than 60% of the radiolabeled glycocalyx was released into the medium by transforming parasites in 3 h and was recovered as high molecular weight material. Parasites labeled with periodate and fluorescein-thiosemicarbazide and then transformed had a corona of fluorescence containing microvilli, much of which was shed onto the slide. Material on cercariae labeled by lodogen-catalyzed iodination was also of high molecular weight and was antigenic. In conclusion, the cercarial glycocalyx appears to be composed of acidic high molecular weight fibrils which are antigenic and incompletely cleared during transformation.

scholarly journals Interactions between neurofilaments and microtubule-associated proteins: a possible mechanism for intraorganellar bridging.

1982 ◽  
Vol 95 (3) ◽  
pp. 982-986 ◽  
Author(s):  
J F Leterrier ◽  
R K Liem ◽  
M L Shelanski
Keyword(s):  
Spinal Cord ◽  
Molecular Weight ◽  
High Molecular Weight ◽  
Microtubule Assembly ◽  
Microtubule Associated Proteins ◽  
Saturable Binding ◽  
In Vitro Assembly ◽  
Associated Proteins ◽  
Brain And Spinal Cord

Mammalian neurofilaments prepared from brain and spinal cord by either of two methods partially inhibit the in vitro assembly of microtubules. This inhibition is shown to be due to the association of a complex of high molecular weight microtubule-associated proteins (MAP1 and MAP2) and tubulin with the neurofilament. Further analysis of the association reveals a saturable binding of purified brain MAPs to purified neurofilaments with a Kd of 10(-7) M. Purified astroglial filaments neither inhibit microtubule assembly nor show significant binding of MAPs. It is proposed that the MAPs might function as one element in a network of intraorganellar links in the cytoplasm.

High molecular weight forms of IGF-II ('big-IGF-II') released by Wilms' tumor cells

1997 ◽  
pp. 396-401 ◽  
Author(s):  
S Schmitt ◽  
Q Ren-Qiu ◽  
T Torresani ◽  
M Doebeli ◽  
J Zapf ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Tumor Cells ◽  
Culture Medium ◽  
Wilms Tumor ◽  
Critical Role ◽  
Polyclonal Antiserum ◽  
Mrna Levels ◽  
Rabbit Polyclonal Antiserum

Insulin-like growth factor-II (IGF-II) is thought to play a critical role in the development of embryonic tumors such as Wilms' tumor. However, despite highly elevated IGF-II mRNA levels in tumors, IGF-II is not elevated in the serum of patients with Wilms' tumors. Recently high molecular weight forms of IGF-II ('big'- or pro-IGF-II) have been found to be produced by some tumors. In order to prove whether or not high molecular weight forms of IGF-II are produced by Wilms' tumor cells and secreted into the culture medium, we established Wilms' tumor cell lines. After column chromatography of the culture medium, IGF-II and pro-IGF-II concentrations were measured. For pro-IGF-II measurement we established a pro-IGF-II RIA using a rabbit polyclonal antiserum directed against amino acids 7-21 (E7-21) of the E-domain of pro-IGF-II. Gel electrophoresis and Western blotting with anti-IGF-II antibodies revealed a band at 7.5 kDa corresponding to fully processed IGF-II and bands between 10 and 20 kDa. Using pro-IGF-II antiserum, bands between 10 and 25 kDa were detected. We conclude that in vitro cultured Wilms' tumor cells produce and release various forms of 'big IGF-II' with molecular masses between 10 and 25 kDa. It remains uncertain whether these high molecular weight forms of IGF-II represent normal precursors of IGF-II or incorrectly processed IGF-II.

scholarly journals Study of the 10-nm-filament fraction isolated during the standard microtubule preparation

1980 ◽  
Vol 191 (2) ◽  
pp. 543-546 ◽  
Author(s):  
A Delacourte ◽  
G Filliatreau ◽  
F Boutteau ◽  
G Biserte ◽  
J Schrevel
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Brain Stem ◽  
Standard Procedure ◽  
Neurofilament Protein ◽  
Associated Proteins ◽  
The Central Nervous System ◽  
10 Nm Filaments ◽  
Membranous Material

The cold non-depolymerizable fractions obtained during the standard procedure for the isolation of microtubules from ox brain stem-cerebral hemispheres and spinal cord have been studied. The cerebral-hemisphere preparation was composed of 10-nm filaments but also contained large amounts of membranes. The polypeptide content included tubulin, microtubule-associated proteins and minor proteins corresponding to the neurofilament triplet of proteins of mol.wt. 210 000, 160 000 and 70 000 respectively. The brain-stem preparation contained more 10-nm filaments than membranes. The polypeptide content consisted of the neurofilament triplet (35%), tubulin (30%) and minor proteins. In contrast, the spinal-cord preparation was mainly composed of 10-nm filaments, free of membranes and containing essentially the neurofilament protein triplet (64%). These filaments appeared very similar to the peripheral-nervous-system neurofilaments described by several authors. Since the best neurofilament from the central nervous system often contained less than 15% of the neurofilament protein triplet, our spinal-cord preparation is an improvement on the usual neurofilament preparation. This simple and rapid method gave large amounts of 10-nm filaments (100 mg per 100 g of spinal cord) characterized by the absence of membranous material, a low content of tubulin and the 50 000-mol.wt.-protein component, and a high content of neurofilament peptides. Thus, the presence of tubulin in 10-nm filament preparations seems to be related to the contaminant membranous material and not to be linked to the interaction in vitro of tubulin or microtubules with neurofilaments, as has been suggested previously.

High molecular weight tau: preferential localization in the peripheral nervous system

1991 ◽  
Vol 100 (1) ◽  
pp. 55-60 ◽  
Author(s):  
I.S. Georgieff ◽  
R.K. Liem ◽  
W. Mellado ◽  
J. Nunez ◽  
M.L. Shelanski
Keyword(s):  
Spinal Cord ◽  
Molecular Weight ◽  
Nervous System ◽  
High Molecular Weight ◽  
Peripheral Nervous System ◽  
Tau Protein ◽  
Protein A ◽  
Amino Terminal ◽  
Neuronal Tissues ◽  
Associated Proteins

Using epitope mapping we have demonstrated that a high molecular weight protein (Mr approximately 115 × 10(3)) present in brain and spinal cord is a member of the tau family of microtubule-associated proteins. Antibodies directed against the amino-terminal, middle and carboxyl-terminal portions of tau recognize this protein. A limited survey of neuronal tissues has shown that this high molecular weight tau protein is present in brain, spinal cord, dorsal root ganglia, dorsal and ventral roots and peripheral nerves. High molecular weight tau protein is expressed at higher levels in spinal cord than in brain and is the only form of tau detected in the adult peripheral nervous system.

scholarly journals Carnosine quenches the reactive carbonyl acrolein in the central nervous system and attenuates autoimmune neuroinflammation

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jan Spaas ◽  
Wouter M. A. Franssen ◽  
Charly Keytsman ◽  
Laura Blancquaert ◽  
Tim Vanmierlo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Effect ◽  
Inflammatory Activity ◽  
Inflammatory Lesions ◽  
The Central Nervous System ◽  
Reactive Carbonyl

Abstract Background Multiple sclerosis (MS) is a chronic autoimmune disease driven by sustained inflammation in the central nervous system. One of the pathological hallmarks of MS is extensive free radical production. However, the subsequent generation, potential pathological role, and detoxification of different lipid peroxidation-derived reactive carbonyl species during neuroinflammation are unclear, as are the therapeutic benefits of carbonyl quenchers. Here, we investigated the reactive carbonyl acrolein and (the therapeutic effect of) acrolein quenching by carnosine during neuroinflammation. Methods The abundance and localization of acrolein was investigated in inflammatory lesions of MS patients and experimental autoimmune encephalomyelitis (EAE) mice. In addition, we analysed carnosine levels and acrolein quenching by endogenous and exogenous carnosine in EAE. Finally, the therapeutic effect of exogenous carnosine was assessed in vivo (EAE) and in vitro (primary mouse microglia, macrophages, astrocytes). Results Acrolein was substantially increased in inflammatory lesions of MS patients and EAE mice. Levels of the dipeptide carnosine (β-alanyl-l-histidine), an endogenous carbonyl quencher particularly reactive towards acrolein, and the carnosine-acrolein adduct (carnosine-propanal) were ~ twofold lower within EAE spinal cord tissue. Oral carnosine treatment augmented spinal cord carnosine levels (up to > tenfold), increased carnosine-acrolein quenching, reduced acrolein-protein adduct formation, suppressed inflammatory activity, and alleviated clinical disease severity in EAE. In vivo and in vitro studies indicate that pro-inflammatory microglia/macrophages generate acrolein, which can be efficiently quenched by increasing carnosine availability, resulting in suppressed inflammatory activity. Other properties of carnosine (antioxidant, nitric oxide scavenging) may also contribute to the therapeutic effects. Conclusions Our results identify carbonyl (particularly acrolein) quenching by carnosine as a therapeutic strategy to counter inflammation and macromolecular damage in MS.

scholarly journals Characterization of immunoreactive somatostatin released from rat nervous system in vitro.

1982 ◽  
Vol 201 (2) ◽  
pp. 321-328 ◽  
Author(s):  
M C Sheppard ◽  
S Hendricks ◽  
A Hudson ◽  
S R Kronheim
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Gel Chromatography ◽  
Nerve Terminals ◽  
Biological Similarity ◽  
The Central Nervous System ◽  
Immunoaffinity Columns ◽  
Somatostatin Immunoreactivity

There is considerable evidence that somatostatin is released from nerve terminals throughout the central nervous system in response to presynaptic stimulation, thus suggesting a neuromodulator role for the peptide. We here report the partial characterization of immunoreactive somatostatin released from rat nervous system in vitro (hypothalamus, spinal cord and hypothalamic, cortical, thalamic and striatal synaptosomes). Serial dilutions of released somatostatin immunoreactivity showed parallelism with dilutions of synthetic somatostatin standard. Somatostatin immunoreactivity released from all tissue areas coeluted with synthetic tetradecapeptide on Sephadex G-25 (fine grade) gel chromatography; more than 85% of this immunoreactivity bound to Sepharose-anti-somatostatin-serum immunoaffinity columns. In addition, immunoreactive material released from hypothalamus, spinal cord and hypothalamic and cortical synaptosomes inhibited somatotropin (growth hormone, ‘STH’, ‘GH’) release from perifused anterior pituitary in a dose-related manner, indicating biological similarity to synthetic somatostatin.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

The Effect of Dextran of Various Molecular Weight on the Coagulation in Dogs

1961 ◽  
Vol 06 (01) ◽  
pp. 015-024 ◽  
Author(s):  
Sven Erik Bergentz ◽  
Oddvar Eiken ◽  
Inga Marie Nilsson
Keyword(s):  
Molecular Weight ◽  
Body Weight ◽  
High Molecular Weight ◽  
Bleeding Time ◽  
Factor Vii ◽  
Low Molecular Weight ◽  
Factor V ◽  
Coagulation Mechanism ◽  
Coagulation Defects

Summary1. Infusions of low molecular weight dextran (Mw = 42 000) to dogs in doses of 1—1.5 g per kg body weight did not produce any significant changes in the coagulation mechanism.2. Infusions of high molecular weight dextran (Mw = 1 000 000) to dogs in doses of 1—1.5 g per kg body weight produced severe defects in the coagulation mechanism, namely prolongation of bleeding time and coagulation time, thrombocytopenia, pathological prothrombin consumption, decrease of fibrinogen, prothrombin and factor VII, factor V and AHG.3. Heparin treatment of the dogs was found to prevent the decrease of fibrinogen, prothrombin and factor VII, and factor V otherwise occurring after injection of high molecular weight dextran. Thrombocytopenia was not prevented.4. In in vitro experiments an interaction between fibrinogen and dextran of high and low molecular weight was found to take place in systems comprising pure fibrinogen. No such interaction occurred in the presence of plasma.5. It is concluded that the coagulation defects induced by infusions of high molecular weight dextran are due to intravascular coagulation.

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