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.

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 Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes

2006 ◽  
Vol 291 (5) ◽  
pp. E1100-E1105 ◽  
Author(s):  
Angela M. Bodles ◽  
Anannya Banga ◽  
Neda Rasouli ◽  
Fumiyo Ono ◽  
Philip A. Kern ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Adipose Tissue ◽  
High Molecular Weight ◽  
Human Adipose Tissue ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Primary Mouse ◽  
Mouse Adipocytes ◽  
Pioglitazone Treatment

Adiponectin is an adipocyte-derived serum protein that plays important roles in energy homeostasis, obesity, and insulin sensitivity. Using sucrose gradients and Western blotting of nondenaturing gels, we examined the adiponectin isoforms secreted from human adipose tissue, human and mouse adipocytes, and cell lines in response to pioglitazone added in vitro. The predominant form secreted from adipose tissue in vitro was the high-molecular-weight (HMW) isoform, with small amounts of low-molecular-weight (LMW) forms present. The addition of pioglitazone (1–3 μM) in vitro increased the secretion of the HMW isoform, with no significant effect on the other isoforms. Human adipose tissue was also examined for changes in adiponectin mRNA levels upon pioglitazone treatment. No difference was detected, suggesting that the effect of pioglitazone is not at the transcriptional level but, rather, at a posttranscriptional phase of the secretory pathway. Additional experiments were conducted to determine whether adiponectin expression was mechanistically similar in other adipose cells. Examination of primary human adipocytes revealed an increase in intracellular HMW isoform with a decline in LMW forms following pioglitazone treatment, with a corresponding increase in the secreted HMW form. Similar results were observed with primary mouse adipocytes, 3T3-F422A cells, and SGBS human adipocyte cells, although differences in the distribution of HMW and LMW isoforms were apparent between cell types. Although there are differences in isoforms between species, in all cases pioglitazone served to increase the secretion of the HMW form of adiponectin.

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.

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals Physicochemical and Antifungal Properties of Clotrimazole in Combination with High-Molecular Weight Chitosan as a Multifunctional Excipient

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 591
Author(s):  
Bożena Grimling ◽  
Bożena Karolewicz ◽  
Urszula Nawrot ◽  
Katarzyna Włodarczyk ◽  
Agata Górniak
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Weight Ratio ◽  
Scanning Calorimetry ◽  
Minimal Inhibitory Concentrations ◽  
Dissolution Tests ◽  
Effective Combination ◽  
The Impact ◽  
High Molecular Weight Chitosan

Chitosans represent a group of multifunctional drug excipients. Here, we aimed to estimate the impact of high-molecular weight chitosan on the physicochemical properties of clotrimazole–chitosan solid mixtures (CL–CH), prepared by grinding and kneading methods. We characterised these formulas by infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry, and performed in vitro clotrimazole dissolution tests. Additionally, we examined the antifungal activity of clotrimazole–chitosan mixtures against clinical Candida isolates under neutral and acid conditions. The synergistic effect of clotrimazole and chitosan S combinations was observed in tests carried out at pH 4 on Candida glabrata strains. The inhibition of C. glabrata growth reached at least 90%, regardless of the drug/excipient weight ratio, and even at half of the minimal inhibitory concentrations of clotrimazole. Our results demonstrate that clotrimazole and high-molecular weight chitosan could be an effective combination in a topical antifungal formulation, as chitosan acts synergistically with clotrimazole against non-albicans candida strains.

scholarly journals Identity and Origin of the ATPase activity associated with neuronal microtubules. I. The ATPase activity is associated with membrane vesicles.

1983 ◽  
Vol 96 (5) ◽  
pp. 1298-1305 ◽  
Author(s):  
D B Murphy ◽  
R R Hiebsch ◽  
K T Wallis
Keyword(s):  
Molecular Weight ◽  
Atpase Activity ◽  
High Molecular Weight ◽  
Brain Tissue ◽  
Membrane Vesicles ◽  
Microtubule Associated Proteins ◽  
In Vitro Assembly ◽  
Microtubule Protein ◽  
Associated Proteins

Microtubule protein purified from brain tissue by cycles of in vitro assembly-disassembly contains ATPase activity that has been postulated to be associated with microtubule-associated proteins (MAPs) and therefore significant for studies of microtubule-dependent motility. In this paper we demonstrate that greater than 90% of the ATPase activity is particulate in nature and may be derived from contaminating membrane vesicles. We also show that the MAPs (MAP-1, MAP-2, and tau factors) and other high molecular weight polypeptides do not contain significant amounts of ATPase activity. These findings do not support the concept of "brain dynein" or of MAPs with ATPase activity.

Interaction of Streptococcus mutans Glucosyltransferases with Teichoic Acids

1980 ◽  
Vol 29 (2) ◽  
pp. 376-382
Author(s):  
H. K. Kuramitsu ◽  
L. Wondrack ◽  
M. McGuinness
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Streptococcus Mutans ◽  
Teichoic Acid ◽  
Lipoteichoic Acid ◽  
Water Soluble ◽  
Heat Inactivation ◽  
Teichoic Acids ◽  
Insoluble Glucan

The Streptococcus mutans GS5 glucosyltransferase activities (both water-soluble and -insoluble glucan-synthesizing fractions) were inhibited by purified lipoteichoic acid. In vitro sucrose-dependent colonization of smooth surfaces by strain GS5 was also markedly reduced in the presence of the amphipathic molecules. The inhibition of soluble glucan synthesis by lipoteichoic acid appeared to be competitive with respect to both sucrose and primer dextran T10. These inhibitory effects were dependent on the presence of the fatty acid components of lipoteichoic acid since deacylated lipoteichoic acids did not inhibit glucosyltransferase activity. However, the deacylated molecules did interact with the enzymes since deacylated lipoteichoic acid partially protected the enzyme activity against heat inactivation and also induced the formation of high-molecular-weight enzyme complexes from the soluble glucan-synthesizing fraction. The presence of teichoic acid in high-molecular-weight aggregates of glucosyltransferase isolated from the culture fluids of strain GS5 was suggested by the detection of polyglycerophosphate in these fractions. In addition to strain GS5, two other organisms containing polyglycerophosphate teichoic acids, Lactobacillus casei and Lactobacillus fermentum , were demonstrated to bind glucosyltransferase activity. These results are discussed relative to the potential role of teichoic acid-glucosyltransferase interactions in enzyme binding to the cell surface of S. mutans and the formation of high-molecular-weight enzyme aggregates in the culture fluids of the organism.

Derivation of the material models for ultra-high molecular-weight polyethylene fiber-reinforced armor-grade composites with different architectures

2016 ◽  
Vol 33 (3) ◽  
Author(s):  
Mica Grujicic ◽  
Jennifer Snipes ◽  
S. Ramaswami ◽  
Vasudeva Avuthu ◽  
Chian-Fong Yen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Design Methodology ◽  
Critical Role ◽  
Fiber Reinforcement ◽  
Mechanical Tests ◽  
Transverse Impact ◽  
Material Models ◽  
Polyethylene Fiber ◽  
Ultra High Molecular Weight

Purpose To overcome the problem of inferior through-the-thickness mechanical properties displayed by armor-grade composites based on 2-D reinforcement architectures, armor-grade composites based on 3D fiber-reinforcement architectures have recently been investigated experimentally. Design/methodology/approach The subject of the present work is armor-grade composite materials reinforced using ultra-high-molecular-weight polyethylene fibers and having four (two 2D and two 3D) prototypical architectures, as well as the derivation of the corresponding material models. The effect of the reinforcement architecture is accounted for by constructing the appropriate unit cells (within which the constituent materials and their morphologies are represented explicitly) and subjecting them to a series of virtual mechanical tests. The results obtained are used within a post-processing analysis to derive and parameterize the corresponding homogenized-material models. One of these models (specifically, the one for 0°/90° cross-collimated fiber architecture) was directly validated by comparing its predictions with the experimental counterparts. The other models are validated by examining their physical soundness and details of their predictions. Lastly, the models are integrated as user-material subroutines, and linked with a commercial finite-element package, in order to carry out a transient non-linear dynamics analysis of ballistic transverse impact of armor-grade composite-material panels with different reinforcement architectures. Findings It is found that the reinforcement architecture plays a critical role in the overall ballistic limit of the armor panel, as well as in its structural and damage/failure response. Originality/value To the authors’ knowledge, the present work is the first reported attempt to assess, computationally, the utility and effectiveness of 3D fiber-reinforcement architectures for ballistic impact applications.

scholarly journals Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1

2018 ◽  
Vol 218 (1) ◽  
pp. 317-332 ◽  
Author(s):  
Li Qiang ◽  
Hong Cao ◽  
Jing Chen ◽  
Shaun G. Weller ◽  
Eugene W. Krueger ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Pancreatic Tumor ◽  
Binding Protein ◽  
Critical Role ◽  
Inverse Correlation ◽  
Pancreatic Tumors ◽  
Matrix Remodeling ◽  
Peripheral Tissues

The process by which tumor cells mechanically invade through surrounding stroma into peripheral tissues is an essential component of metastatic dissemination. The directed recruitment of the metalloproteinase MT1-MMP to invadopodia plays a critical role in this invasive process. Here, we provide mechanistic insight into MT1-MMP cytoplasmic tail binding protein 1 (MTCBP-1) with respect to invadopodia formation, matrix remodeling, and invasion by pancreatic tumor cells. MTCBP-1 localizes to invadopodia and interacts with MT1-MMP. We find that this interaction displaces MT1-MMP from invadopodia, thereby attenuating their number and function and reducing the capacity of tumor cells to degrade matrix. Further, we observe an inverse correlation between MTCBP-1 and MT1-MMP expression both in cultured cell lines and human pancreatic tumors. Consistently, MTCBP-1–expressing cells show decreased ability to invade in vitro and metastasize in vivo. These findings implicate MTCBP-1 as an inhibitor of the metastatic process.

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