CHAPTER 3 – Anatomy, Physiology, and Biochemistry of the Rabbit

The pathogenesis of the acute exanthems; an interpretation based on experimental investigations with mousepox; infectious ectromelia of mice.

Smallpox was one of the most devastating diseases known to humanity. Although smallpox was eradicated through a historically successful vaccination campaign, there is concern in the global community that either Variola virus (VARV), the causative agent of smallpox, or another species of Orthopoxvirus could be used as agents of bioterrorism. Therefore, development of countermeasures to Orthopoxvirus infection is a crucial focus in biodefense research, and these efforts rely on the use of various animal models. Smallpox typically presented as a generalized pustular rash with 30 to 40% mortality, and although smallpox-like syndromes can be induced in cynomolgus macaques with VARV, research with this virus is highly restricted; therefore, animal models with other orthopoxviruses have been investigated. Monkeypox virus causes a generalized vesiculopustular rash in rhesus and cynomolgus macaques and induces fatal systemic disease in several rodent species. Ectromelia virus has been extensively studied in mice as a model of orthopoxviral infection in its natural host. Intranasal inoculation of mice with some strains of vaccinia virus produces fatal bronchopneumonia, as does aerosol or intranasal inoculation of mice with cowpox virus. Rabbitpox virus causes pneumonia and fatal systemic infections in rabbits and can be naturally transmitted between rabbits by an aerosol route similar to that of VARV in humans. No single animal model recapitulates all known aspects of human Orthopoxvirus infections, and each model has its advantages and disadvantages. This article provides a brief review of the Orthopoxvirus diseases of humans and the key pathologic features of animal models of Orthopoxvirus infections.

https://journals.sagepub.com/doi/pdf/10.1177/0300985810378649

Animal Models of Orthopoxvirus Infection

Received March 26, 2008; accepted June 5, 2008. 

The development of durable mechanical circulatory support systems paralleled the expansion of cardiac transplantation. The National Institutes of Health sponsored grants in the 1980s to develop implantable left heart assist systems; 20 years later, they contracted for a national registry, the Interagency Registry for Mechanical Assisted Circulatory Support, to track the clinical evolution of this new technology. The Interagency Registry for Mechanical Assisted Circulatory Support has refined the classification of New York Heart Association class IV heart failure, standardized adverse event definitions, and explored outcomes of device type, location, and strategy. The majority of mechanical circulatory support patients are between the ages of 50 and 70 years, and ≈90% of patients are in the highest levels of clinical instability before implantation. Six-month survival after device implant is 75%, but it increases to 80% among those not in shock at implantation. Patients who require biventricular support have decreased survival. As longer-term outcomes are analyzed, improved outcomes may justify triage of high-risk patients awaiting heart transplantation to chronic mechanical circulatory support.

The application of mechanical circulatory support in animal experiments can be traced back to the work of Carrel and Lindberg in the 1930s.1,2 With the initial foray into open-heart surgery in the 1950s,3,4 the stage was set for application of more prolonged mechanical support for myocardial recovery in situations of failure to wean from cardiopulmonary bypass. Although initial reports of successful recovery used roller-pump technology,5 their applicability was limited by issues of blood trauma and difficulties in modulation of pump speed in response to changes in left atrial and left ventricular pressure. The first clinical application of a pneumatically driven ventricular assist device (VAD) is attributed to DeBakey in 1966, in which a 37-year-old woman was successfully supported for 10 …

Mechanical Circulatory Support Registering a Therapy in Evolution

INFECTION of human beings by chromobacteria is a relatively rare occurrence. Hence, it has been of considerable interest in the past six months to observe in this hospital 11 cases of infection by these organisms, one of which had a fatal termination with bacterial endocarditis. The chromobacteria have been described as nonsporulating, aerobic bacilli, usually motile and usually Gram-negative, producing yellow, red, or violet pigment which is generally insoluble in water. The bacteria are ordinarily saprophytic and are commonly found in water, soil, and sewage. They grow abundantly and with ease on ordinary mediums, and their most arresting feature is the pigment production, which occurs only in the presence of oxygen, usually only on solid mediums at suitable temperatures, and is most abundant on the primary culture. 1 The chief member of the group producing a violet pigment is Chromobacterium violaceum, that of the group producing pink or red pigment

INFECTION DUE TO CHROMOBACTERIA: Report of Eleven Cases

A lethal dwarf mutation in the rabbit with stigmata of endocrine abnormality.

http://science.sciencemag.org/content/sci/81/2088/25.full.pdf

A lethal mutation in the rabbit with stigmata of an acromegalic disorder.

Experiments are reported in which it was shown that rabbits which had recovered from experimental or spontaneous rabbit pox were refractory to inoculation of pox virus injected by various routes, and in addition did not develop clinical manifestations of the disease under conditions of exposure to florid cases of pox. It was found that pox recovered rabbits were susceptible to inoculation with the virus of virus III disease of rabbits and that virus III recovered rabbits could be successfully inoculated with pox virus. Furthermore, virus III recovered rabbits developed pox when subjected to room exposure in the same manner as did normal rabbits. It thus appears that there is no specific relationship between the two viruses. Rabbits which had recovered from experimental or spontaneous pox were found to be just as susceptible to inoculation with the virus of infectious myxoma of rabbits as were normal rabbits, a result which demonstrates that there is no specific relationship between these viruses. Rabbits which had recovered from experimental or spontaneous pox were refractory to inoculation with culture dermovaccine virus, but vaccine recovered rabbits were not completely refractory to inoculation with pox virus. Under conditions of exposure to clinical cases of pox, adult vaccine immune rabbits did not develop clinical manifestations of pox, but young, recently weaned vaccinated rabbits did contract mild but definite clinical pox. Experimental pox recovered rabbits were partially refractory to inoculation with neurovaccine virus and neurovaccine recovered rabbits were partially refractory to inoculation with pox virus. The refractory condition of the pox immune rabbits appeared to be more pronounced than that of the neurovaccine immunes. The cutaneous lesions which developed from the intradermal injection of pox, neurovaccine, and culture vaccine viruses showed definite differences with respect to the rate and persistence of active growth, amount of edema, hemorrhage, and necrosis, and the degree of tissue destructiveness. These features were most pronounced in the lesions of pox virus and were least marked in the lesions of culture vaccine virus. The differences were particularly apparent in normal rabbits, but they were also present in the lesions which developed in immune animals. It was found that the calf was susceptible to inoculation with pox virus applied to a scarified skin area. There were many similarities in the appearance and course of the pox lesions to those resulting from culture vaccine virus, the New York Board of Health vaccine, and neurovaccine virus similarly inoculated. But the pox lesions were most numerous, much the largest and most destructive, and by far the most persistent while next in order were those of the Board of Health dermovaccine. The results of these various experiments showed that a close relationship obtains between pox virus, on the one hand, and vaccine virus and neurovaccine virus, on the other, but it cannot be said that pox virus is identical in all respects with either one of these viruses. The findings indicated that the relationship between pox and neurovaccine viruses is closer than that between pox and culture vaccine viruses. Upon the basis of the results observed in culture (dermo) vaccine immune rabbits inoculated with or exposed to pox, it appeared that vaccination with vaccine virus offered a method of protection against rabbit pox.

https://rupress.org/jem/article-pdf/63/3/353/1180677/353.pdf

Studies on the etiology of rabbit pox iii. tests of the relation of rabbit pox virus to other viruses by crossed inoculation and exposure experiments

A filterable agent was isolated from 7 cases of spontaneous rabbit pox by the intratesticular injection in rabbits of a variety of tissues. The virus was transmitted for 15 consecutive testicle to testicle passages in rabbits by Berkefeld V filtrates of testicular tissue emulsions. Unfiltered emulsions were more potent than filtrates. The virulence of the virus was maintained by ice box storage of infected tissues for as long as 127 days. The pathogenic properties of the virus persisted under conditions of animal passage for the 9 months from January to October, 1933, covered by these studies. The reaction produced in rabbits by the inoculation of tissue-virus emulsions was of two principal types, the first of which has been described and analyzed in the present paper. In the case of intratesticular injections, particularly of testicular tissue inocula, an acute fulminating and rapidly fatal condition regularly developed. The outstanding features were a massive hemorrhagic orchitis with marked scrotal edema, fever, and death within a week. The second type of reaction which is taken up in the next paper of this series (1) was observed under conditions in which the animal survived a week or longer. Occasional examples occurred in rabbits of the so called intratesticular series. The reaction was characterized by the development of a disease syndrome with a diversity of clinical manifestations which, it may be stated here for the sake of continuity, was indistinguishable from spontaneous rabbit pox.

/pdf/studies-on-the-etiology-of-rabbit-pox-i-isolation-of-a-2zwxxocou8.pdf

Studies on the etiology of rabbit pox : i. isolation of a filterable agent: its pathogenic properties.

The clinical manifestations and course of disease observed in experimental rabbit pox have been described and analyzed The condition differed from the acute fulminating and rapidly fatal type of experimental infection (1) in that the period of survival was longer, a variety of clinical manifestations developed and a considerable proportion of the cases recovered The most conspicuous symptom was a generalized papular eruption on the skin and mucocutaneous borders The production of the disease was associated with routes of inoculation other than the intratesticular or with a small dosage The majority of cases were inoculated with Berkefeld V filtrates of tissue-virus emulsions and not with the more potent unfiltered emulsions The local reactions resulting from various routes of inoculation were described Of special interest were the pronounced cutaneous reactions induced by intradermal injection, the high instance of marked clinical manifestations after intravenous inoculation, the failure of lesions to localize in the lines of scarification of skin and cornea even in cases with a profuse cutaneous eruption, and the development of cytoplasmic inclusion bodies in the epithelial cells of the cornea following scarification and conjunctival instillation of virus In the character of its clinical manifestations and course of disease, experimental rabbit pox was indistinguishable from cases of the spontaneous pox

https://rupress.org/jem/article-pdf/63/2/259/1180673/259.pdf

Studies on the etiology of rabbit pox ii. clinical characteristics of the experimentally induced disease

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