Publications by authors named "Tamburini P"

Article Synopsis
  • Tarperprumig (ALXN1820) is a bispecific antibody designed to treat conditions caused by dysregulated activity in the complement alternative pathway, usable via small volume injections either under the skin or intravenously.
  • It consists of two variable domains that target properdin and human serum albumin, showing a high binding affinity and forming a stable complex.
  • The antibody effectively inhibits key processes related to complement pathway activation and is currently undergoing clinical development for relevant disorders.
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Article Synopsis
  • Gefurulimab (ALXN1720) is a bispecific antibody designed for subcutaneous treatment of chronic disorders linked to the activation of the terminal complement pathway by blocking the breakdown of complement component 5 (C5).
  • It consists of specialized antibody fragments derived from llamas and humans that bind tightly to C5 and human serum albumin (HSA), enabling it to inhibit complement activity effectively in lab assays.
  • Structural studies indicate that gefurulimab obstructs C5's interaction with its activating convertase, suggesting it is a strong candidate for treating complement-mediated disorders.
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Article Synopsis
  • - This study investigates how immune complexes form when patients are exposed to two different anti-C5 antibodies simultaneously, focusing on the transition from one treatment to another.
  • - Researchers used size exclusion chromatography and multiangle light scattering to analyze the interactions between eculizumab and two other anti-C5 antibodies (TPP-2799 and TP-3544), both of which bind C5 similarly.
  • - Results showed that when mixed with other antibodies, the complexes formed could exceed 1500 kDa, indicating multiple antibodies and C5 molecules interacting, suggesting the need for careful monitoring and strategies to prevent complex formation during such treatment transitions.
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In this work, a flexible and extensive digital platform for Smart Homes is presented, exploiting the most advanced technologies of the Internet of Things, such as Radio Frequency Identification, wearable electronics, Wireless Sensor Networks, and Artificial Intelligence. Thus, the main novelty of the paper is the system-level description of the platform flexibility allowing the interoperability of different smart devices. This research was developed within the framework of the operative project HABITAT (Home Assistance Based on the Internet of Things for the Autonomy of Everybody), aiming at developing smart devices to support elderly people both in their own houses and in retirement homes, and embedding them in everyday life objects, thus reducing the expenses for healthcare due to the lower need for personal assistance, and providing a better life quality to the elderly users.

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Background: When aiming at studying and monitoring locomotor development in childhood, innovative indexes for the characterization of motor control performance and wearable technologies have highlighted the potential of significant advances. In particular, quantitative assessment of motor performance during natural walking (NW) and tandem walking (TW) has been proposed to highlight manifestations of motor automaticity and complexity, respectively.

Research Question: This work aims at providing a quantitative overview of metrics characterizing locomotor maturation in a typically developing population, by analysing NW and TW.

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When aiming at assessing motor control development, natural walking (NW), and tandem walking (TW) are two locomotor tasks that allow analyzing different characteristics of motor control performance. NW is the reference locomotor task, expected to become more and more automatic with age. TW is a nonparadigmatic task used in clinics to highlight eventual impairments and to evaluate how a child deals with a new challenging motor experience.

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Eculizumab, a monoclonal antibody (mAb) directed against complement protein C5, is considered to be the current standard of care for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. This study describes the generation and preclinical attributes of ALXN1210, a new long-acting anti-C5 mAb, obtained through select modifications to eculizumab to both largely abolish target-mediated drug disposition (TMDD) and increase recycling efficiency via the neonatal Fc receptor (FcRn). To attenuate the effect of TMDD on plasma terminal half-life (t1/2), histidine substitutions were engineered into the complementarity-determining regions of eculizumab to enhance the dissociation rate of the mAb:C5 complex in the acidic early endosome relative to the slightly basic pH of blood.

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The availability of wearable sensors allows shifting gait analysis from the traditional laboratory settings, to daily life conditions. However, limited knowledge is available about whether alterations associated to different testing environment (e.g.

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The assessment of walking function alterations is a key issue to design effective rehabilitative interventions in sub-acute stroke patients. Nevertheless, the objective quantification of these alterations remains a challenge. Clinical rating scales are commonly used in clinical practice, but have been proven prone to errors associated to the evaluator subjective perception.

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Background: In the rat brain, a single intracerebroventricular injection of neuraminidase from Clostridium perfringens induces ependymal detachment and death. This injury occurs before the infiltration of inflammatory blood cells; some reports implicate the complement system as a cause of these injuries. Here, we set out to test the role of complement.

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Background: Eculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement-mediated hemolysis associated with paroxysmal nocturnal hemoglobinuria (PNH). The molecular basis for the poor response to eculizumab in a small population of Japanese patients is unclear.

Methods: We assessed the sequences of the gene encoding C5 in patients with PNH who had either a good or poor response to eculizumab.

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C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition.

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Carbonic anhydrase IX (CAIX) is a cell surface glycoprotein that is expressed in many different tumors and yet restricted in normal tissues to the gastrointestinal tract. It is upregulated by hypoxia and correlates with tumor grade and poor survival in several tumor indications. Monoclonal antibodies (mAb) with single digit nanomolar binding affinity for CAIX were derived by panning with the recombinant ectodomain of CAIX against the MorphoSys HUCAL Gold library of human Fabs.

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While activation of serum complement mediates antibody-initiated vascular allograft injury, increasing evidence indicates that complement also functions as a modulator of alloreactive T cells. We tested whether blockade of complement activation at the C5 convertase step affects T cell-mediated cardiac allograft rejection in mice. The anti-C5 mAb BB5.

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Thrombopoietin (TPO) receptor agonists lacking sequence homology to TPO were designed by grafting a known peptide sequence into the hinge and/or kappa constant regions of a human anti-anthrax antibody. Some of these proteins were equipotent to TPO in stimulating cMpl-r activity in vitro and in increasing platelet levels in vivo. ALXN4100TPO (4100TPO), the best agonist in this series with a K(d) of 30 nM for cMpl-r, exhibited potent activity as a radiation countermeasure in CD2F1 mice exposed to lethal total-body radiation from a cobalt-60 γ-ray source.

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We have characterized comprehensive transcript and proteomic profiles of cell lines corresponding to normal breast (MCF10A), noninvasive breast cancer (MCF7) and invasive breast cancer (MDA-MB-231). The transcript profiles were first analysed by a modified protocol for representational difference analysis (RDA) of cDNAs between MCF7 and MDA-MB-231 cells. The majority of genes identified by RDA showed nearly complete concordance with microarray results, and also led to the identification of some differentially expressed genes such as lysyl oxidase, copper transporter ATP7A, EphB6, RUNX2 and a variant of RUNX2.

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Interconversion of estrogens by osteoblasts may play a role in regulating bone mass. As a first step toward exploring this possibility, we investigated the expression and activity of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in cultured human osteoblasts (HOB) and osteoblast-like osteosarcoma cells (MG63, TE85, and SaOS-2). Significant 17beta-HSD activity was detected in cell-free extracts of all bone cells with oxidation of estradiol to estrone predominating over reduction.

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We reported previously the cloning of a novel human serine protease inhibitor containing two Kunitz-like domains, designated as placental bikunin, and the subsequent purification of a natural counterpart from human placental tissue (Marlor, C. W., Delaria, K.

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Interrogation of the public expressed sequence tag (EST) data base with the sequence of preproaprotinin identified ESTs encoding two potential new members of the Kunitz family of serine protease inhibitors. Through reiterative interrogation, an EST contig was obtained, the consensus sequence from which encoded both of the novel Kunitz domains in a single open reading frame. This consensus sequence was used to direct the isolation of a full-length cDNA clone from a placental library.

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A murine model of disseminated candidiasis involving intranasal challenge with Candida albicans was developed and used to explore the role of C. albicans aspartic proteases as virulence factors during early dissemination. Pretreatment of neutropenic mice with the aspartic protease inhibitor pepstatin A by intraperitoneal injection afforded strong dose-dependent protection against a subsequent lethal intranasal dose of an aspartic protease-producing strain (ATCC 32354) of C.

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The protein sequence of cytotoxic T-lymphocyte antigen-2 beta (CTLA-2 beta) is 36% identical to the proregion of mouse cathepsin L (Denizot, F., Brunet, J.F.

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Conversion of dansyl-Tyr-Val-Gly to dansyl-Tyr-Val-NH2 by recombinant type A rat 75-kDa peptidylglycine alpha-amidating enzyme (alpha-AE) is inactivated by ascorbate, dehydroascorbate, and hydrogen peroxide in a time- and concentration-dependent manner. Both ascorbate- and dehydroascorbate-mediated inactivation are saturable with apparent kinact/Kinact values of 1.7 and 0.

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A rapid sensitive method for the quantification of in vitro HIV-protease activity has been developed on the basis of the endoproteolytic conversion of N-Dns-SQ-NYPIV to N-Dns-SQNY. The use of the N-dansyl group as a fluorescence label was shown to not significantly alter the apparent kinetic parameters for the peptide-enzyme interaction. Using fluorescence detection, the dansylated product and unconverted substrate are detected in a single rapid (3 min) isocratic reverse-phase HPLC separation in quantities as low as 0.

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The kinetic parameters were obtained for enzymatic alpha-amidation of peptides of the form N-dansyl-(Gly)4-X-Gly-OH, in which the amino acid at position X was substituted with each of the 20 natural amino acids. The enzyme used in these studies was a highly enriched preparation of alpha-amidating enzyme secreted by a clonal (CA-77) cell line which actively expresses mature alpha-amidated peptides. A 130-fold and 11-fold variation respectively in apparent Km and Vmax values was observed.

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