Modulation of peritoneal macrophage effector functions in the early stage of Mesocestoides corti (Cestoda) infection in mice

The activation of peritoneal macrophage effector functions after therapy with free PZQ and PZQ incorporated in liposomes (lip.PZQ) was studied in the Mesocestoides corti–mouse model system. Each drug formulation was administered to an infected group of mice in 6 daily doses from day 14 p.i. Phagocytic activity of macrophages increased significantly after the administration of both drug formulations, more after lip.PZQ with an earlier peak observed for PZQ (day 3) than for lip.PZQ (day 6). Empty liposomes had no significant effect. The average counts of ingested particles in phagocytosing cells were significantly higher only after lip.PZQ administration. The pattern of changes in phagocytic activity correlated with the reduction of parasite numbers in the peritoneal cavity, with the highest observed on day 6 after therapy with lip.PZQ. Phagocytosis of lip.PZQ in vivo stimulated significantly the respiratory burst in peritoneal macrophages, with the highest concentration of superoxide anions recorded on day 1 after the last dose, whereas therapy with PZQ itself did not increase this process significantly. The capacity for the respiratory burst declined in all groups with progressing infection. It is proposed that the phagocytic activity of peritoneal macrophages after therapy was stimulated indirectly as a consequence of activation of the specific immune response. The larvicidal effect of lip.PZQ on the tetrathyridia in the peritoneal cavity was synergistic with the phagocytic activity and might be the result of double action of drug and superoxide anions generated during the respiratory burst stimulated by this drug formulation.

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Topical resiquimod can induce disease regression and enhance T-cell effector functions in cutaneous T-cell lymphoma

Blood ◽

10.1182/blood-2015-02-630335 ◽

2015 ◽

Vol 126 (12) ◽

pp. 1452-1461 ◽

Cited By ~ 86

Author(s):

Alain H. Rook ◽

Joel M. Gelfand ◽

Maria Wysocka ◽

Andrea B. Troxel ◽

Bernice Benoit ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Early Stage ◽

Skin Lesions ◽

Cutaneous T Cell Lymphoma ◽

Cell Recruitment ◽

Effector Functions ◽

Cell Clones ◽

Key Points ◽

Cell Effector

Key Points Topical resiquimod is a safe, effective therapy for early-stage CTCL that can clear both treated and untreated skin lesions. Responding patients had T-cell recruitment into skin, enhanced T-cell effector functions, and eradication of the malignant T-cell clones.

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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Automated high-resolution microscopy: the approaches so far

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100125312 ◽

1987 ◽

Vol 45 ◽

pp. 58-61

Author(s):

W. O. Saxton

Keyword(s):

High Resolution ◽

Early Stage ◽

Automatic Recording ◽

Microprocessor Control ◽

Alternative Systems ◽

Electron Image ◽

Complete Automation ◽

Analysis System ◽

High Resolution Microscopy

Recent commercial microscopes with internal microprocessor control of all major functions have already demonstrated some of the benefits anticipated from such systems, such as continuous magnification, rotation-free diffraction and magnification, automatic recording of mutually registered focal series, and fewer control knobs. Complete automation of the focusing, stigmating and alignment of a high resolution microscope, allowing focal series to be recorded at preselected focus values as well, is still imminent rather than accomplished, however; some kind of image pick-up and analysis system, fed with the electron image via a TV camera, is clearly essential for this, but several alternative systems and algorithms are still being explored. This paper reviews the options critically in turn, and stresses the need to consider alignment and focusing at an early stage, and not merely as an optional extension to a basic proposal.

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Direct observation of Fe-Al-Zn ternary intermetallic compound and its transformation during the early stage of hot-dip galvanizing

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100151416 ◽

1993 ◽

Vol 51 ◽

pp. 1116-1117

Author(s):

C. S. Lin ◽

W. A. Chiou ◽

M. Meshii

Keyword(s):

Intermetallic Compound ◽

Reaction Rate ◽

Diffusion Rate ◽

Early Stage ◽

Zinc Bath ◽

Steel Sheets ◽

Direct Observations ◽

Solid Iron ◽

Iron And Zinc ◽

Ternary Intermetallic Compound

The galvannealed steel sheets have received ever increased attention because of their excellent post-painting corrosion resistance and good weldability. However, its powdering and flaking tendency during press forming processes strongly impairs its performance. In order to optimize the properties of galvanneal coatings, it is critical to control the reaction rate between solid iron and molten zinc.In commercial galvannealing line, aluminum is added to zinc bath to retard the diffusion rate between iron and zinc by the formation of a thin layer of Al intermetallic compound on the surface of steel at initial hot-dip galvanizing. However, the form of this compound and its transformation are still speculated. In this paper, we report the direct observations of this compound and its transformation.The specimens were prepared in a hot-dip simulator in which the steel was galvanized in the zinc bath containing 0.14 wt% of Al at a temperature of 480 °C for 5 seconds and was quenched by liquid nitrogen.

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Anisotropy of interfacial defects in the initial stage of MOVPE GaAs growth On Si

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100176095 ◽

1990 ◽

Vol 48 (4) ◽

pp. 592-593

Author(s):

C. Vannuffel ◽

C. Schiller ◽

J. P. Chevalier

Keyword(s):

Early Stage ◽

Threading Dislocations ◽

Mbe Growth ◽

Detailed Mechanism ◽

Si Substrates ◽

Initial Stage ◽

Interfacial Defects ◽

Interfacial Dislocations ◽

Step Growth ◽

Essential Problem

Recently, interest has focused on the epitaxy of GaAs on Si as a promising material for electronic applications, potentially for integration of optoelectronic devices on silicon wafers. The essential problem concerns the 4% misfit between the two materials, and this must be accommodated by a network of interfacial dislocations with the lowest number of threading dislocations. It is thus important to understand the detailed mechanism of the formation of this network, in order to eventually reduce the dislocation density at the top of the layers.MOVPE growth is carried out on slightly misoriented, (3.5°) from (001) towards , Si substrates. Here we report on the effect of this misorientation on the interfacial defects, at a very early stage of growth. Only the first stage, of the well-known two step growth process, is thus considered. Previously, we showed that full substrate coverage occured for GaAs thicknesses of 5 nm in contrast to MBE growth, where substantially greater thicknesses are required.

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Metabolic engineering of CHO cells to prepare glycoproteins

Emerging Topics in Life Sciences ◽

10.1042/etls20180056 ◽

2018 ◽

Vol 2 (3) ◽

pp. 433-442 ◽

Cited By ~ 1

Author(s):

Qiong Wang ◽

Michael J. Betenbaugh

Keyword(s):

Metabolic Engineering ◽

Cho Cells ◽

Genetic Manipulation ◽

Chinese Hamster ◽

Post Translational Modification ◽

Effector Functions ◽

Recombinant Glycoproteins ◽

Production Platform ◽

Chemical Inhibitors ◽

Amino Acid Mutations

As a complex and common post-translational modification, N-linked glycosylation affects a recombinant glycoprotein's biological activity and efficacy. For example, the α1,6-fucosylation significantly affects antibody-dependent cellular cytotoxicity and α2,6-sialylation is critical for antibody anti-inflammatory activity. Terminal sialylation is important for a glycoprotein's circulatory half-life. Chinese hamster ovary (CHO) cells are currently the predominant recombinant protein production platform, and, in this review, the characteristics of CHO glycosylation are summarized. Moreover, recent and current metabolic engineering strategies for tailoring glycoprotein fucosylation and sialylation in CHO cells, intensely investigated in the past decades, are described. One approach for reducing α1,6-fucosylation is through inhibiting fucosyltransferase (FUT8) expression by knockdown and knockout methods. Another approach to modulate fucosylation is through inhibition of multiple genes in the fucosylation biosynthesis pathway or through chemical inhibitors. To modulate antibody sialylation of the fragment crystallizable region, expressions of sialyltransferase and galactotransferase individually or together with amino acid mutations can affect antibody glycoforms and further influence antibody effector functions. The inhibition of sialidase expression and chemical supplementations are also effective and complementary approaches to improve the sialylation levels on recombinant glycoproteins. The engineering of CHO cells or protein sequence to control glycoforms to produce more homogenous glycans is an emerging topic. For modulating the glycosylation metabolic pathways, the interplay of multiple glyco-gene knockouts and knockins and the combination of multiple approaches, including genetic manipulation, protein engineering and chemical supplementation, are detailed in order to achieve specific glycan profiles on recombinant glycoproteins for superior biological function and effectiveness.

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