Richard B. Hornick

Fecal Leukocytes in Diarrheal Illness

Abstract Stools from subjects with diarrhea were examined microscopically for leukocytes, using methylene blue stain. The study included 169 patients: 114 volunteers who ingested known enteric path...

Biological properties of Norwalk agent of acute infectious nonbacterial gastroenteritis.

Summary Acute infectious nonbacterial gastroenteritis was induced in adult volunteers through three serial passages by oral administration of bacteria-free stool filtrates. This suggested that a replicating agent of subbacterial size was responsible for the observed disease. The biophysical properties of the agent, as assayed in volunteers, were consistent with those of a small virus, most closely related to the parvovirus group among known animal viruses. The agent appeared to have a diameter less than 66 nm and likely less than 36 nm. It appeared to lack a lipid containing envelope and was acid stable. It was stable to heating at 60° for 30 min. The agent appeared to be relatively host specific for man and conferred at least short-term immunity. Because of the high frequency of disease induced in unselected volunteers, widespread natural immunity to this agent may be absent or perhaps incomplete. Preliminary evidence suggested that the Norwalk agent replicated in an in vitro system, human fetal intestinal organ culture. We gratefully acknowledge the cooperation of the volunteers and staff at the Maryland State House of Correction. We also thank Drs. David Fedson and Sheldon Wolff of the Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, for their help with the study, Dr. Samuel Formal of the Walter Reed Army Institute of Medical Research for performing enterotoxin assays and monkey inoculations, and Dr. Robert Purcell of the Laboratory of Infectious Diseases for performing Australia antigen determinations.

Specificity of protection of man immunized against sporozoite-induced falciparum malaria.

During a period of 421 days a total of 1,441 X-irradiated mosquitoes inoculated attenuated sporozoites of Burma (Thau.) strain Plasmodium falciparum into a volunteer. Strict ethical guidelines were followed. The volunteer was also exposed at various times to nonirradiated mosquitoes carrying infective sporozoites of the same strain and of strains from Malaya, Panama and the Philippines, and did not develop falciparum malaria. Following exposure to nonirradiated mosquitoes carrying Chesson strain P. vivax, he developed vivax malaria. Antisporozoite antibody, demonstrated by the circumsporozoite precipitation test, appeared in his serum and reacted equally against the Burma strain of P. falciparum and strains from Malaya, Panama and the Solomon Islands, but did not react with Chesson vivax sporozoites.

Immunity of cholera in man: relative role of antibacterial versus antitoxic immunity.

Purified cholera toxoid is antigenic when given enterally and orally. Purified toxoid fails to provide protection against experimental challenge. Clinical cholera confers formidable protection against homologous or heterologous rechallenge. Failure to culture vibrios from intestinal fluid or stool of re-challenge volunteers suggests that the predominant immune mechanism is antibacterial rather than antitoxic.

Comparative Pyrogenic Reactivity of Rabbit and Man to Bacterial Endotoxin

Summary Comparative reactivity of mature albino rabbits (1.8–2.2 kg) and of healthy man to the pyrogenic activity of purified S. typhosa, E. coli, and Pseudomonas endotoxins is presented. On a per kilogram basis, rabbit and man are approximately equally reactive to threshold pyrogenic quantities of endotoxin. When larger doses of endotoxin are employed, the dose-response relationships become considerably steeper for man. On a total dose basis, rabbits require smaller quantities of endotoxin to elicit threshold febrile responses, but as total toxin dose is increased, febrile responses of man rapidly exceed those of the rabbit. Subjective toxic responses of man parallel the pyrogenic responses. These data provide a more definitive base line for interpreting studies with bacterial endotoxin that involve extrapolation of rabbit febrile responses to man.

Acute Infectious Nonbacterial Gastroenteritis: Etiology and Pathogenesis

Abstract Acute infectious nonbacterial gastroenteritis is a common syndrome of obscure cause. Although widespread epidemiological and clinical data point to an infectious cause, etiologic agents ha...

Influenza antibody in human respiratory secretions after subcutaneous or respiratory immunization with inactivated virus.

STUDIES with human volunteers have shown that experimental infection with influenza virus is a better stimulus of antibody in respiratory secretions than is subcutaneous immunization with inactivated vaccine, although both procedures result in the production of similar concentrations of serum antibody1,2. The work reported here was undertaken to determine if administration of inactivated virus vaccine through the respiratory tract provokes a similar antibody response in respiratory secretions.

The role of endotoxin during typhoid fever and tularemia in man: IV. The integrity of the endotoxin tolerance mechanisms during infection

Volunteers infected with Salmonella typhosa develop a remarkable hyperreactivity to the pyrogenic and subjective toxic activities of homologous (S. typhos) and heterologous (Pseudomonas) endotoxins. The present studies quantitate this augmented reactivity and demonstrate by three differing approaches that significant tolerance to these endotoxins can be readily induced within the framework of the hyperreactive state. Thus, (a) tolerance induced before illness by repeated daily intravenous injections of the endotoxins remained demonstrable during overt illness, (b) daily intravenous injections of the endotoxins begun during overt illness evoked progressively increasing tolerance, and (c) continuous intravenous infusions of S. typhosa endotoxin during illness rapidly induced a pyrogenic refractory state. Despite unequivocal activation of the endotoxin tolerance mechanisms by any of the above methods, the febrile and toxic course of typhoid fever proceeded unabated. Similarly, in other volunteers with Pasteurella tularensis infection, continuous intravenous infusions of S. typhosa endotoxin evoked initial hyperreactive febrile and subjective toxic responses followed by rapid appearance of a pyrogenic refractory state without modification of the underlying clinical illness. These observations suggest that circulating endotoxin plays no major role in pathogenesis of the sustained fever and toxemia during typhoid fever and tularemia in man. The mechanisms responsible for the systemic hyperreactivity to endotoxin during typhoid fever and tularemia were further investigated. Low grade endotoxemia, nonspecific effects of tissue injury, impaired ability of the reticuloendothelial system to clear circulating endotoxin, and production of cytophilic antibodies capable of sensitizing leukocytes to endotoxin did not appear responsible. Inflammatory reactions to intradermal S. typhosa endotoxin increased significantly during typhoid fever. However, since no such dermal hyperreactivity developed to Pseudomonas endotoxin during typhoid fever nor to S. typhosa endotoxin during tularemia, the systemic hyperreactivity to bacterial endotoxins during typhoid fever and tularemia could not presently be ascribed to enhanced levels of acquired hypersensitivity.

Mucociliary Function during Experimentally Induced Rhinovirus Infection in Man

In conjunction with a controlled study of the effect of vitamin C on susceptibility to experimentally induced rhinovirus infections in man, we have conducted a study of nasal mucociliary function in the subjects volunteering for the study. In the 21 volunteers an average mucociliary flow rate (measured by the Quinlan tagged particle technique) of 7.5 mm/min was found in those with normal nasal morphology and 4.0 mm/min in those with abnormal nasal morphology. The rates decreased during infection in both groups but at different times after induction of infection. Ascorbic acid had no effect on either susceptibility to induced rhinovirus infection or mucociliary transport.

Lack of enhanced oxygen consumption by polymorphonuclear leukocytes on phagocytosis of virulent Salmonella typhi.

Human polymorphonuclear leukocytes exhibit an enhanced rate of oxygen consumption during phagocytosis of relatively avirulent strains of Salmonella typhi or Staphylococcus aureus. However, phagocytosis of a virulent strain of Salmonella typhi is not associated with augmented oxygen consumption. The ability of a bacterial strain to alter the postphagocytic rate of oxygen consumption of polymorphonuclear leukocytes may be related to its in vivo virulence.