Karl Otto Landsteiner (1868-1943). Physician-biochemist-immunologist.

Karl Landsteiner applied the sciences of biochemistry, pathology, microbiology, and immunology in medical research to great success during the first half of the 20th century. Although he is principally known for elucidating the major blood group antigens A and B and their isoantibodies for which he was awarded the Nobel Prize in Physiology or Medicine, Landsteiner made many other important medical discoveries. In that respect, he ascertained that paralytic poliomyelitis was due to a virus, the pancreas was damaged in cystic fibrosis, simple chemicals called haptens were able to combine with antibodies, and the Rh antigen that was later found to be the principal cause of hemolytic anemia of the newborn was found in most humans.

Franklin Delano Roosevelt's (FDR's) (1882-1945) 1921 neurological disease revisited; the most likely diagnosis remains Guillain-Barré syndrome.

In 2003, we published evidence that the most likely cause of FDR's 1921 neurological disease was Guillain-Barré syndrome. Afterwards, several historians and neurologists stated in their publications that FDR had paralytic poliomyelitis. However, significant criticism of our article or new support for that diagnosis was not revealed.

Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury.

Introduction: Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries.

Methods: Sheep were randomized to a sham-injured control group (n=6) or ALI/sepsis group (n=7).

Time profile of oxidative stress and neutrophil activation in ovine acute lung injury and sepsis.

The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure after acute lung injury and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation injury and instillation of live Pseudomonas aeruginosa into both lungs.

Cardiopulmonary effects of low-dose arginine vasopressin in ovine acute lung injury.

Objective: To elucidate the effects of low-dose arginine vasopressin on cardiopulmonary functions and nitrosative stress using an established model of acute lung injury.

Design: Prospective, randomized, controlled laboratory experiment.

Setting: Investigational intensive care unit.

The therapeutic test: an ancient malady in the 21st century.

The response to treatment was the diagnostic mainstay in ancient times when diseases were poorly understood. Now that the bases of most diseases are known, appropriate diagnostic means are available. However, many physicians still rely on therapeutic tests to establish diagnoses.

Time course of nitric oxide synthases, nitrosative stress, and poly(ADP ribosylation) in an ovine sepsis model.

Introduction: Different isoforms of nitric oxide synthases (NOS) and determinants of oxidative/nitrosative stress play important roles in the pathophysiology of pulmonary dysfunction induced by acute lung injury (ALI) and sepsis. However, the time changes of these pathogenic factors are largely undetermined.

Methods: Twenty-four chronically instrumented sheep were subjected to inhalation of 48 breaths of cotton smoke and instillation of live Pseudomonas aeruginosa into both lungs and were euthanized at 4, 8, 12, 18, and 24 hours post-injury.

Birth of the science of immunology.

The science of immunology emerged in the last of the 19th and the first of the 20th century. Substantial progress in physics, chemistry and microbiology was essential for its development. Indeed, microorganisms became one of the principal investigative tools of the major founders of that science - Louis Pasteur, Robert Koch, Ilya Ilich Metchnikoff, Paul Ehrlich and Jules Bordet.

Jules Bordet (1870-1961): a bridge between early and modern immunology.

Jules Bordet, a pioneering immunologist, lived until the dawn of molecular immunology. He was born in Belgium in 1870, obtained a medical degree in 1892, worked at l'Institut Pasteur in Paris from 1894 to 1901 and then established the Pasteur Institute of Brabant in Brussels. Before World War I, Bordet found that complement binds to antibody-antigen complexes regardless of the antigen or antibodies involved.

Molecular biological effects of selective neuronal nitric oxide synthase inhibition in ovine lung injury.

Neuronal nitric oxide synthase is critically involved in the pathogenesis of acute lung injury resulting from combined burn and smoke inhalation injury. We hypothesized that 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, blocks central molecular mechanisms involved in the pathophysiology of this double-hit insult. Twenty-five adult ewes were surgically prepared and randomly allocated to 1) an uninjured, untreated sham group (n = 7), 2) an injured control group with no treatment (n = 7), 3) an injury group treated with 7-nitroindazole from 1-h postinjury to the remainder of the 24-h study period (n = 7), or 4) a sham-operated group subjected only to 7-nitroindazole to judge the effects in health.

Inhibition of lung permeability changes after burn and smoke inhalation by an anti-interleukin-8 antibody in sheep.

Purpose: To evaluate the effects of a monoclonal antibody against interleukin-8 (K2.2) on the microvascular fluid flux after combined injury by burn and smoke inhalation.

Methods: Fourteen sheep were prepared surgically by placing a lung lymph catheter and a flank lymph catheter to examine the microvascular fluid flux.

Pulmonary expression of nitric oxide synthase isoforms in sheep with smoke inhalation and burn injury.

Previous studies have indicated increased plasma levels of inducible nitric oxide synthase in lung. This study further examines the pulmonary expression of nitric oxide synthase (NOS) isoforms in an ovine model of acute lung injury induced by smoke inhalation and burn injury (S+B injury). Female range bred sheep (4 per group) were sacrificed at 4, 8, 12, 24, and 48 hours after injury and immunohistochemistry was performed in tissues for various NOS isoforms.

Inhibition of neuronal nitric oxide synthase in ovine model of acute lung injury.

Objective: Acute respiratory distress syndrome/acute lung injury is a serious complication of burn patients with concomitant smoke inhalation injury. Nitric oxide has been shown to play a major role in pulmonary dysfunction from thermal damage. In this study, we have tested the hypothesis that inhibition of neuronal nitric oxide synthase could ameliorate the severity of acute lung injury using our well-established ovine model of cutaneous burn and smoke inhalation.

gamma-Tocopherol nebulization by a lipid aerosolization device improves pulmonary function in sheep with burn and smoke inhalation injury.

Fire accident victims who sustain both thermal injury to skin and smoke inhalation have gross evidence of systemic and pulmonary oxidant damage and acute lung injury. We hypothesized that gamma-tocopherol (gT), a reactive O(2) and N(2) scavenger, when delivered into the airway, would attenuate lung injury induced by burn and smoke inhalation. Acute lung injury was induced in chronically prepared, anesthetized sheep by 40% total burn surface area, third-degree skin burn and smoke insufflation (48 breaths of cotton smoke, <40 degrees C).

Ilya Ilich Metchnikoff (1845-1915) and Paul Ehrlich (1854-1915): the centennial of the 1908 Nobel Prize in Physiology or Medicine.

Ilya Metchnikoff and Paul Ehrlich shared the 1908 Nobel Prize in Physiology or Medicine - Metchnikoff for discovering the major types and functions of phagocytes and Ehrlich for discovering the types of blood leukocytes, helping to uncover how to generate and use antibodies to protect against bacterial toxins, and formulating the receptor concept of antibodies binding to antigens. In 1908 phagocytic and humoral defences were thought to be unrelated but it was realized much later that they influence one other. Thus, it is fitting that the 1908 Nobel Laureates in Physiology or Medicine remain closely connected in the minds of modern immunologists.

Neuronal nitric oxide synthase inhibition attenuates cardiopulmonary dysfunctions after combined burn and smoke inhalation injury in sheep.

Objective: We hypothesized that nitric oxide derived from the neuronal nitric oxide synthase (NOS) is responsible for much of the injury resulting from skin burn and smoke inhalation. Therefore, we aimed to examine the effects of selective neuronal NOS inhibition on cardiopulmonary functions and cellular injury in sheep with acute respiratory distress syndrome secondary to combined burn and smoke inhalation injury.

Design: Prospective, randomized, controlled laboratory experiment.

Novel ovine model of methicillin-resistant Staphylococcus aureus-induced pneumonia and sepsis.

Methicillin-resistant Staphylococcus aureus (MRSA)-related pneumonia and/or sepsis are a frequent serious menace. The aim of the study was to establish a standardized and reproducible model of MRSA-induced septic pneumonia to evaluate new therapies. Sheep were operatively prepared for chronic study.

Arteriovenous CO2 removal improves survival compared to high frequency percussive and low tidal volume ventilation in a smoke/burn sheep acute respiratory distress syndrome model.

Unlabelled: OBJECTIVES AND SUMMARY BACKGROUND: Low tidal volume ventilation (LTV) has improved survival with acute respiratory distress syndrome (ARDS) by reducing lung stretch associated with volutrauma and barotrauma. Additional strategies to reduce lung stretch include arteriovenous carbon dioxide removal (AVCO2R), and high frequency percussive ventilation (HFPV). We performed a prospective, randomized study comparing these techniques in our clinically relevant LD100 sheep model of ARDS to compare survival, pathology, and inflammation between the 3 ventilator methods.

Abraham Lincoln's Gettysburg illness.

When Abraham Lincoln delivered the Gettysburg Address, he was weak and dizzy; his face had a ghastly colour. That evening on the train to Washington, DC, he was febrile and weak, and suffered severe headaches. The symptoms continued; back pains developed.

Acute bronchial obstruction in sheep: histopathology and gland cytokine expression.

An ovine model of smoke inhalation and burn (S+B) injury models the pathophysiology of these injuries in humans. This study examines the degree of airway obstruction, associated histopathology, and bronchial gland cell expression of cytokines during the first 24 hours after S+B injury in sheep. Changes in the mean degree of obstruction were limited to the bronchial airways, showing significant increases in obstruction with time, P<.

The inhibition of inducible nitric oxide synthase in ovine sepsis model.

Excessive NO has been shown to play a major role in the pathogenesis of multiple organ dysfunctions in septic condition. Burn injury, especially if it is associated with smoke inhalation, is often complicated by subsequent development of pneumonia or sepsis that determine the outcome. In the present study, we developed an ovine sepsis model, created by exposing sheep to smoke inhalation followed by instillation of bacteria into the airway, that closely mimics human sepsis and pneumonia.

Combined burn and smoke inhalation injury impairs ovine hypoxic pulmonary vasoconstriction.

Objective: To examine the effects of combined burn and smoke inhalation injury on hypoxic pulmonary vasoconstriction, 3-nitrotyrosine formation, and respiratory function in adult sheep.

Design: Prospective, placebo-controlled, randomized, single-blinded trial.

Setting: University research laboratory.

Lipopolysaccharide protection from oxygen toxicity: effect on rat pulmonary selectins.

Sublethal doses of LPS result in increased tolerance to high concentrations of oxygen and this is associated with decreased pulmonary inflammation in a rat model. To investigate the mechanism of decreased neutrophil influx into the lung in this model, we measured levels of mRNA in the lung for the endothelial adhesion molecules, E-selectin and P-selectin. Immunostaining for E-selectin protein was also done in rat lungs, as well as measurement of soluble L-selectin in the blood.