Digoxin antibody fragments have little therapeutic benefit in yew tree poisoning

1990 ◽  
Vol &NA; (725) ◽  
pp. 15
Author(s):  
&NA;
Author(s):  
U. Aebi ◽  
L.E. Buhle ◽  
W.E. Fowler

Many important supramolecular structures such as filaments, microtubules, virus capsids and certain membrane proteins and bacterial cell walls exist as ordered polymers or two-dimensional crystalline arrays in vivo. In several instances it has been possible to induce soluble proteins to form ordered polymers or two-dimensional crystalline arrays in vitro. In both cases a combination of electron microscopy of negatively stained specimens with analog or digital image processing techniques has proven extremely useful for elucidating the molecular and supramolecular organization of the constituent proteins. However from the reconstructed stain exclusion patterns it is often difficult to identify distinct stain excluding regions with specific protein subunits. To this end it has been demonstrated that in some cases this ambiguity can be resolved by a combination of stoichiometric labeling of the ordered structures with subunit-specific antibody fragments (e.g. Fab) and image processing of the electron micrographs recorded from labeled and unlabeled structures.


2019 ◽  
Author(s):  
Antoine Maruani ◽  
Peter A. Szijj ◽  
Calise Bahou ◽  
João C. F. Nogueira ◽  
Stephen Caddick ◽  
...  

<p>Diseases are multifactorial, with redundancies and synergies between various pathways. However, most of the antibody-based therapeutics in clinical trials and on the market interact with only one target thus limiting their efficacy. The targeting of multiple epitopes could improve the therapeutic index of treatment and counteract mechanisms of resistance. To this effect, a new class of therapeutics emerged: bispecific antibodies.</p><p>Bispecific formation using chemical methods is rare and low yielding and/or requires a large excess of one of the two proteins to avoid homodimerisation. In order for chemically prepared bispecifics to deliver their full potential, high-yielding, modular and reliable cross-linking technologies are required. Herein, we describe a novel approach not only for the rapid and high-yielding chemical generation of bispecific antibodies from native antibody fragments, but also for the site-specific dual functionalisation of the resulting bioconjugates. Based on orthogonal clickable functional groups, this strategy enables the assembly of functionalised bispecifics with controlled loading in a modular and convergent manner.</p>


2017 ◽  
Vol 68 (2) ◽  
pp. 354-357 ◽  
Author(s):  
Andrei Niculae ◽  
Cristiana David ◽  
Razvan Florin Ion Dragomirescu ◽  
Ileana Peride ◽  
Flavia Liliana Turcu ◽  
...  

Once recombinant human erythropoietin (r-HuEPO) was introduced in daily practice, huge steps were made in combating the adverse effects induced by anemia in chronic kidney disease population. Still, r-HuEPO resistance and the doses ensuring the maximum therapeutic benefit remain matters of debate. The aim of our study was to assess the correlation between the presence and the degree of inflammation and the r-HuEPO requirements in chronic dialysis patients. We conducted a 2 years prospective study on 146 patients undergoing chronic dialysis treated with r-HuEPO. Based on their average CRP (C-reactive protein) levels, obtained from repeated samplings at 3 months interval, 3 groups were formed; we noted in each group the average values of r-HuEPO prescribed to achieve the optimum hemoglobin levels according to the dialysis best practice guidelines and all the adverse effects of the therapy. A direct correlation was observed between CRP levels and r-HuEPO requirements in the first 2 groups of patients (CRP under 6 mg/L and CRP values 6-20 mg/L), with significant increase in r-HuEPO doses between groups (p [ 0.001); the third group, CRP values over 20 mg/dL, showed a minor, insignificant increase in average r-HuEPO doses compared to mild inflammation group (p = 0.199) and more adverse effects of the therapy (p [ 0.05). Inflammation is an important determinant of anemia in chronic dialysis patients and can induce an increase in the doses of r-HuEPO. However, prescribing excessive r-HuEPO doses is not the answer in severe inflammatory status, due to lack of response and possible adverse effects.


2017 ◽  
Vol 63 (3) ◽  
pp. 497-505
Author(s):  
Vadim Pokrovskiy ◽  
Yelena Lukasheva ◽  
Nikolay Chernov ◽  
Yelena Treshchalina

The effectiveness of L-lysine-alpha oxidase Trichoderma cf. Aureoviride Rifai BKMF-4268D (LO) on models of subcutaneous xenografts of human tumors in athymic mice as well as the effectiveness of combination therapy with known antitumor drugs: cisplatin, irinotecan, etoposide on models of P388 lymphocytic leukemia, Lewis lung (LLC) and B16 melanoma was evaluated. The intraperitoneal injection of LO in a discrete regime at doses of 150-75-75-75-75 E/kg demonstrated inhibition of growth of all studied xenografts of human tumors in athymic mice. The combination of irinotecan+LO on the LLC model gave a significant summative therapeutic benefit with an increase in mouse life expectancy up to 35%. Cisplatin and LO realized a significant (p


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