Selective occlusion of tumor vasculature was tested as a therapy for solid tumors in a mouse model. The formation of blood clots (thrombosis) within the tumor vessels was initiated by targeting the cell surface domain of human tissue factor, by means of a bispecific antibody, to an experimentally induced marker on tumor vascular endothelial cells. This truncated form of tissue factor (tTF) had limited ability to initiate thrombosis when free in the circulation, but became an effective and selective thrombogen when targeted to tumor endothelial cells. Intravenous administration of the antibody-tTF complex to mice with large neuroblastomas resulted in complete tumor regressions in 38 percent of the mice.
SummaryTargeting exposed anionic phospholipids on a spectrum of virus-infected cells can protect against lethal virus infections in vivo.
Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. We report that four human anti-phospholipid monoclonal antibodies (mAbs) (PGN632, P1, IS4, and CL1) inhibit HIV-1 CCR5-tropic (R5) primary isolate infection of peripheral blood mononuclear cells (PBMCs) with 80% inhibitory concentrations of <0.02 to ∼10 µg/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1α and MIP-1β. The release of these β-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes.
The methods for aluminum analysis vary from the simple and often nonspecific chemical and physical procedures to the highly sophisticated types such as neutron activation and atomic absorption spectrometry. Atomic absorption procedures are the techniques of choice for most routine hospital laboratories. The wide distribution of aluminum in nature can create severe contamination problems in aluminum analysis. Procedures to avoid contamination are discussed. In recent years aluminum has been implicated as a possible etiological agent in DES and in Alzheimer's Disease. A common finding in these two conditions is an elevated brain aluminum content. The patients with Alzheimer's Disease develop characteristic neurofibrillary tangles which lead to the degeneration of the affected neurons. Similar tangles can be induced in laboratory animals injected intracerebrally with aluminum salts. Even though the laboratory animals develop tangles resembling those seen in patients with Alzheimer's Disease, no evidence has been published to show that the tangles seen in Alzheimer's Disease are induced by the elevated brain aluminum content. Although there are some similar clinical symptoms in both Alzheimer's Disease and DES, the hemodialysis patients with DES do not develop neurofibrillary tangles despite an elevated brain aluminum content. The significance of this difference is not understood. The sources of the increase in tissue aluminum levels found in hemodialysis patients are from the gastrointestinal absorption of aluminum in aluminum containing phosphate-binding gels and by transfer from the dialyzate to the blood during the hemodialysis procedure. Plasma aluminum values may be reduced by the administration of a minimum dosage of phosphate-binding gels and by the use of purified water to make up the dialysate. The incidence of DES is reduced by the use of these procedures to maintain the hemodialysis patients' plasma aluminum at a low concentration. The increased brain aluminum content of patients with Alzheimer's Disease is derived from the environment. Because of the ubiquitous occurrence of aluminum, we are exposed to it daily in our food, water, and in the air. The low levels of aluminum absorbed from the environment may explain why susceptible patients do not develop Alzheimer's Disease until after many years of exposure, if indeed aluminum is the etiological agent in Alzheimer's Disease. The many papers that have been published concerning aluminum, DES, and Alzheimer's Disease make a strong case for linking elevated tissue aluminum content with these conditions. However, conclusive evidence to support this theory has not been published. Until the effect of aluminum on cellular chemistry is more fully understood, the possibility that DES and Alzheimer's Disease may result from other causes or from aluminum and another agent acting concomitantly must be considered.
This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world.
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