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A centennial review: The 1890 tetanus antitoxin paper of von Behring and Kitasato and the related developments
Abstract
The significance of the 1890 tetanus antitoxin paper by von Behring and Kitasato in the development of a new discipline, immunology, is reviewed. The possible reasons why Kitasato lost the first Nobel Prize for medicine to von Behring are presented. These are as follows: (1) The Nobel selection committee literally interpreted Alfred Nobel's will to award the prize to “the person who has made the most important discovery.” (2) In the late 19th century, diphtheria was a serious contagious disease which claimed many thousands of lives in the Europe and America; and von Behring's solely authored paper on diphtheria antitoxin clinched the award for him. (3) The merit of tetanus antitoxin to humans, which was the focal point of the 1890 paper on tetanus antitoxin jointly authored by von Behring and Kitasato, was not recognized at the time of the award in 1901; it became apparent only during the First World War.
... Behring was awarded the first Nobel Prize in Physiology and Medicine in 1901 "for his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and deaths" [8]. There were 46 nominees for the first Nobel Prize in Medicine in 1901, which included Kitasato, Ehrlich, Golgi, Koch, and Ramó n y Cajal, amongst others, but Behring was nominated officially and became the first winner of the Nobel Prize in Physiology or Medicine; Kitasato never appeared in the list of nominees again [9]. ...
... By the late 1920s, the chemical nature of antibodies was not yet known. In 1923; one of Avery's pupils, Michael Heidelberger (1888-1991, who is considered one of the founders of immunohistochemistry, determined that the antibodies made against pneumococcal polysaccharides were proteins [13] (Fig. 3a). In experiments conducted during the early 1930s, Heidelberger and his postdoctoral fellows Forrest E. Kendall (1899-1987) (later Professor Emeritus of Biochemistry at Columbia University) and Elvin A. Kabat (Kabatchnick) were able to measure the amount of antibody in washed antigen-antibody precipitates and developed the first antigen-antibody complex identified microscopically by means of attaching a purple azo dye to the antigen. ...
Immunohistochemistry is an extraordinary and extensively used technique whereby antibodies are used to detect antigens in cells within a tissue section. It has numerous applications in medicine, particularly in cancer diagnosis. It was Albert Hewett Coons, Hugh J Creech, Norman Jones, and Ernst Berliner who conceptualized and first implemented the procedure of immunofluorescence in 1941. They used fluorescein isothiocyanate (FITC)-labelled antibodies to localize pneumococcal antigens in infected tissues. Since then, with improvement and development of protein conjugation, enzyme labels have been introduced, such as peroxidase and alkaline phosphatase. The history of immunohistochemistry (IHC) combines physiology, immunology, biochemistry, and the work of various Nobel Prize laureates. From von Behring who was awarded de first Nobel Prize in 1901 for his work on serum therapy to the 1984 Nobel Prize for the discovery of monoclonal antibodies by Milstein, Kohler, and Jerne, IHC is a story of cooperation and collaboration which led to the development of this magnificent technique that is used daily in anatomical pathology laboratories worldwide.
... This microorganism was early recognized as the causative agent of the disease in 1821, and fully identified by Klebs and Loeffler in 1833, hence its vernacular name of 'Klebs-Loeffler bacillus' (Loeffler, 1884;Park and Williams 1896). The toxigenic potential of the bacterium was studied by von Behring and Kitasato in 1890 (Kantha 1991), in fact the bacteria antitoxin developed by the German physiologist was described to save the life of a small child on Christmas 1891, in Berlin, as recorded in 'An Apocryphal Christmas Miracle'; von Behring was awarded the first Nobel Prize in Physiology and Medicine in 1901 "for his work on serum therapy, especially its application against diphtheria…", whereas Kitasato, who was also nominated for a shared Nobel Prize, in the same year, did not receive the recognition. ...
Virulence attenuation, the ‘weakening’ of the pathogenic ability of an
organism that prevents it from causing disease while still remaining alive,
constitutes one of the most effective approaches in vaccine development
against either bacterial or viral diseases. This technique has the advantage
of eliciting good immunological memory responses, as compared to
vaccines elaborated with dead bacteria, but also has the drawback of
potentially being more dangerous, as some organisms can revert in
virulence and cause disease. The phenomenon of virulence attenuation was
discovered in the 19th century and still remains currently in use; present
studies aim to develop new ways of attenuation, with the goal of
generating less virulent bacterial strains that closely resemble the original
pathogenic organism, hence capable of eliciting good immunity, but
innocuous to the people who receive them as vaccines. The present chapter
reviews the use of relevant attenuated bacterial vaccines for the prevention
of a variety of diseases, caused by either Gram-positive or Gram-negative
bacteria.
... These virulence blockers are usually antibodies, unlike most inhibitors in development. Such virulence blockers have been well researched and have been in use since the late 19th century [24,25]. Recently, specific molecules have been developed that inhibit the formation of cholera toxins and biofilms in Vibrio cholerae [26,27]. ...
The overuse of antibiotics has led to severe bacterial drug resistance. Blocking pathogen virulence devices is a highly effective approach to combating bacterial resistance worldwide. Type three secretion systems (T3SSs) are significant virulence factors in Gram-negative pathogens. Inhibition of these systems can effectively weaken infection whilst having no significant effect on bacterial growth. Therefore, T3SS inhibitors may be a powerful weapon against resistance in Gram-negative bacteria, and there has been increasing interest in the research and development of T3SS inhibitors. This review outlines several reported small-molecule inhibitors of the T3SS, covering those of synthetic and natural origin, including their sources, structures, and mechanisms of action.
... The mAb field has seen considerable progress since Emil von Behring and Shibasaburo Kitasato discovered antibodies in the 1890s. mAbs have the ability to target a wide variety of microbial organisms, including bacteria, viruses, parasites, fungi, and toxins [7]. Various mAbs are being used to conduct clinical trials against pathogenic viruses, including HIV and SARS-CoV-2 which, together, account for more than 40% of clinical trials ( Figure 2). ...
Monoclonal antibodies (mAbs), the new revolutionary class of medications, are fast becoming tools against various diseases thanks to a unique structure and function that allow them to bind highly specific targets or receptors. These specialized proteins can be produced in large quantities via the hybridoma technique introduced in 1975 or by means of modern technologies. Additional methods have been developed to generate mAbs with new biological properties such as humanized, chimeric, or murine. The inclusion of mAbs in therapeutic regimens is a major medical advance and will hopefully lead to significant improvements in infectious disease management. Since the first therapeutic mAb, muromonab-CD3, was approved by the U.S. Food and Drug Administration (FDA) in 1986, the list of approved mAbs and their clinical indications and applications have been proliferating. New technologies have been developed to modify the structure of mAbs, thereby increasing efficacy and improving delivery routes. Gene delivery technologies, such as non-viral synthetic plasmid DNA and messenger RNA vectors (DMabs or mRNA-encoded mAbs), built to express tailored mAb genes, might help overcome some of the challenges of mAb therapy, including production restrictions, cold-chain storage, transportation requirements, and expensive manufacturing and distribution processes. This paper reviews some of the recent developments in mAb discovery against viral infections and illustrates how mAbs can help to combat viral diseases and outbreaks.
... Clostridial neurotoxins, such as botulinum toxin (BoNT) and tetanus toxin (TeNT), have long been known to dysregulate muscle contractile function [117][118][119]. However, the clinical symptoms of botulism and tetanus are very different. ...
Synaptic transmission is essential for controlling motor functions and maintaining brain functions such as walking, breathing, cognition, learning, and memory. Neurotransmitter release is regulated by presynaptic molecules assembled in active zones of presynaptic terminals. The size of presynaptic terminals varies, but the size of a single active zone and the types of presynaptic molecules are highly conserved among neuromuscular junctions (NMJs) and central synapses. Three parameters play an important role in the determination of neurotransmitter release properties at NMJs and central excitatory/inhibitory synapses: the number of presynaptic molecular clusters, the protein families of the presynaptic molecules, and the distance between presynaptic molecules and voltage-gated calcium channels. In addition, dysfunction of presynaptic molecules causes clinical symptoms such as motor and cognitive decline in patients with various neurological disorders and during aging. This review focuses on the molecular mechanisms responsible for the functional similarities and differences between excitatory and inhibitory synapses in the peripheral and central nervous systems, and summarizes recent findings regarding presynaptic molecules assembled in the active zone. Furthermore, we discuss the relationship between functional alterations of presynaptic molecules and dysfunction of NMJs or central synapses in diseases and during aging.
A good name is defined as a person's positive reputation. Thus, the present research presents Biblical verses describing this concept: 'A good name is better than good oil' (Ecclesiastes 7:1), and 'A good name is rather to be chosen than great riches, and loving favor rather than silver and gold' (Proverbs 22:1).
This research explores the diverse facets of a good name, such as writing effective abstracts, exemplary medical practitioners, the esteemed status of nurses, the dignity of midwifery, the reputation of hospitals, missionary medicine, notable individuals, missionary medicine, volunteers vital work, parenting styles, and good friends.
Evaluating from a contemporary perspective, a good name encompasses various types, including doctors, nurses, midwives, notable figures, parents, good friends, and Nobel Prize laureates.
The Research suggests that having a good name, or being known for one's integrity and positive traits, is valuable and admirable.
A good name embodies honorable traits that contribute to humanity. Thus, throughout the long years of our existence, a good name has been a constant companion.
The remarkable impact of antibiotics on human health is being eroded at an alarming rate by the emergence of multidrug resistant pathogens. There is a recognised consensus that new strategies to tackle infection are urgently needed to limit the devasting impact of antibiotic resistance on our global healthcare infrastructure. Next generation antimicrobials (NGAs) are compounds that target bacterial virulence factors to disrupt pathogenic potential without impacting bacterial viability. By disabling the key virulence factors required to establish and maintain infection, NGAs make pathogens more vulnerable to clearance by the immune system and can potentially render them more susceptible to traditional antibiotics. In this review, we discuss the developing field of NGAs and how advancements in this area could offer a viable standalone alternative to traditional antibiotics or an effective means to prolong antibiotic efficacy when used in combination.
Louis Pasteur's work initiated the birth of microbiology in Denmark. Carl Julius Salomonsen was the pioneer who inspired and taught Christian Gram, Thorvald Madsen and Bernhard Bang bacteriological techniques at his annual bacteriological course which he started in 1883 at the University of Copenhagen. These pioneers developed Danish human and veterinary microbiology and became world famous. Emil Chr. Hansen developed Danish technical/industrial microbiology in the Carlsberg Laboratory and purified yeast and designed equipment for propagation of pure yeast which was used world-wide in beer brewing. He also became world famous. The fascinating birth and development of Danish microbiology is summarized in this article, which is dedicated to the 200 years birthday of Louis Pasteur December 27th and 100 years birthday of the Danish Pasteur Society October 25th , 2022.
Le sepsis est la 3eme cause de mortalité dans les pays occidentaux, avec un taux de mortalité entre 20 et 50% selon la sévérité. La « prédiction » du devenir clinique du patient est essentielle pour établir le traitement le plus adéquat. Quelques protéines marqueurs de l'inflammation ou d'une infection (CRP, procalcitonine) sont citées pour le suivi des patients en clinique mais manquent de spécificité pour le sepsis. D'autre part, les études « omiques » ont permis de générer des listes de biomarqueurs potentiels du pronostic vital du sepsis. En revanche, aucun n'a encore été validé et/ou confirmé en fonction de la gravité du sepsis et du devenir du patient. Il faut pour cela accéder non seulement à des cohortes de patients parfaitement caractérisées et également disposer de méthodes quantitatives robustes et validées. La spectrométrie de masse apporte une capacité de spécificité et de multiplexage à haut niveau qui permettait de confirmer l'intérêt d'une ou plusieurs de ces protéines dans le cas du pronostic du sepsis. Les dosages immunologiques apportent quant à eux en plus de la sensibilité et de la spécificité, une mise en œuvre en routine clinique simple et rapide. Dans un premier temps, une liste de biomarqueurs identifiés avec des cohortes de patients a été établie d’après la littérature. Puis, des méthodes de quantification de ces biomarqueurs ont été développées. Nous nous sommes intéressés d’une part à quantifier les calgranulines dans le plasma en développant des ELISA et des méthodes de spectrométrie de masse par des approches bottom-up et top-down. D’autre part, deux méthodes de quantification multiplexes ont été développées par spectrométrie de masse avec et sans étape d’immunopurification en fonction des concentrations des protéines présentes dans le plasma afin de vérifier la pertinence de la liste de biomarqueurs potentiels. Toutes ces méthodes ont été appliquées à une cohorte de 49 patients atteints de choc septique.
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