Necrotizing Meningoencephalitis in Atypical Dog Breeds: A Case Series and Literature Review

Background

Canine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led to the presumption that it is a breed‐restricted disorder.

Hypothesis/Objectives

Our objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported.

Animals

Four dogs with NME.

Methods

Archives from 3 institutions and from 1 author''s (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated.

Results

Necrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate‐to‐severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents.

Conclusions and Clinical Importance

Until now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed‐restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.     

Comparison of the cardiorespiratory effects of medetomidine-butorphanol-ketamine and medetomidine-butorphanol-midazolam in patas monkeys (Erythrocebus patas).

The cardiorespiratory effects, effectiveness, and reversibility of two injectable anesthetic combinations were compared in captive patas monkeys (Erythrocebus patas). Seven patas monkeys were hand-injected with medetomidine (40 microg/kg, i.m.), butorphanol (0.4 mg/kg. i.m.), and ketamine (3.0 mg/kg. i.m.), and seven were injected with the same dosages of medetomidine and butorphanol plus midazolam (0.3 mg/kg, i.m.). Heart rates decreased in monkeys in both treatment groups and were lower than those previously recorded in patas monkeys anesthetized with either ketamine or ketamine and isoflurane. Mean arterial pressures were highest in ketamine-treated monkeys but remained within normal limits for both groups. End tidal CO2 values increased gradually over time in both groups and were above physiologic norms after 20 min. Respiratory rates were similar between groups and remained constant throughout the procedures. Despite adequate ventilation parameters, initial low percent oxygen-hemoglobin saturation (SpO2) values were suggestive of severe hypoxemia. It was not clear whether these were accurate readings or an artifact of medetomidine-induced peripheral vasoconstriction. Oxygen supplementation restored SpO2 values to normal (>94%) in both groups. Both combinations effectively produced a state of light anesthesia, although spontaneous recoveries occurred after 30 min in three ketamine-treated monkeys. All monkeys were given i.m. atipamezole (0.2 mg/kg) and naloxone (0.02 mg/kg), whereas midazolam-treated monkeys also received flumazenil (0.02 mg/kg, i.v.), which resulted in faster (median recovery time = 5 min) and more complete recoveries in this group. Both combinations are safe to use when supplemented with oxygen, although the midazolam combination provided a longer anesthetic period and was more fully reversible.     

Autophagy genes are essential for dauer development and life-span extension in C. elegans

Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans.     

Secretion of human interferons by yeast

Plasmids were constructed to direct synthesis of the human interferons IFN-alpha 1, IFN-alpha 2, and IFN-gamma in the yeast Saccharomyces cerevisiae. Expression of IFN genes containing coding sequences for secretion signals resulted in the secretion of IFN activity. A large proportion of the IFN-alpha 1 and IFN-alpha 2 isolated from the yeast cell growth media had the same amino termini as the natural mature interferons, suggesting a removal of the signal sequences identical to that of human cells. These results show that a lower eukaryote, such as yeast, can utilize and process a human signal sequence.     

Rapid identification of nonessential genes of herpes simplex virus type 1 by Tn5 mutagenesis

The large genome of herpes simplex virus type of (HSV-1) encodes at least 80 polypeptides, the majority of which have no recognized function. A subgroup of these gene products appears to be nonessential for virus replication in cell culture, but contributes to the complex life cycle of the virus in the host. To identify such functions, a simple insertional mutagenesis method has been used for selective inactivation of individual HSV-1 genes. The bacterial transposon Tn5 was allowed to insert randomly into cloned restriction fragments representing the entire short unique (US) region of the HSV-1 genome. Of the 12 open reading frames that were mutagenized with Tn5, mutant derivatives of US2, US4, and US5 were recombined into the virus. These three genes proved to be nonessential for HSV-1 replication in Vero (African Green monkey kidney) cells and the US4 gene appeared to be involved in viral pathogenesis in the central nervous system of mice. This rapid mutagenesis procedure should prove useful in exploring the entire HSV-1 genome as well as the genomes of other complex animal viruses.     

Very-Long-Baseline Radio Interferometry: The Mark III System for Geodesy, Astrometry, and Aperture Synthesis

The Mark III very-long-baseline interferometry (VLBI) system allows recording and later processing of up to 112 megabits per second from each radio telescope of an interferometer array. For astrometric and geodetic measurements, signals from two radio-frequency bands (2.2 to 2.3 and 8.2 to 8.6 gigahertz) are sampled and recorded simultaneously at all antenna sites. From these dual-band recordings the relative group delays of signals arriving at each pair of sites can be corrected for the contributions due to the ionosphere. For many radio sources for which the signals are sufficiently intense, these group delays can be determined with uncertainties under 50 picoseconds. Relative positions of widely separated antennas and celestial coordinates of radio sources have been determined from such measurements with 1 standard deviation uncertainties of about 5 centimeters and 3 milliseconds of arc, respectively. Sample results are given for the lengths of baselines between three antennas in the United States and three in Europe as well as for the arc lengths between the positions of six extragalactic radio sources. There is no significant evidence of change in any of these quantities. For mapping the brightness distribution of such compact radio sources, signals of a given polarization, or of pairs of orthogonal polarizations, can be recorded in up to 28 contiguous bands each nearly 2 megahertz wide. The ability to record large bandwidths and to link together many large radio telescopes allows detection and study of compact sources with flux densities under 1 millijansky.     

Cell-surface changes after infection with oncogenic viruses: requirement for synthesis of host DNA

The change in the surface structure of cultutred mammalian cells infected with oncogenic DNA viruses was similar to that described for the fully and permanently transformed cell surfaces. The course of appearance of this change was established. Synthesis of host DNA is required for expression of the surface change triggered by infection with the oncogenic virus.     

Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus

A group of rats was trained to escape low-intensity shock in a shuttle-box test, while another group of yoked controls could not escape but was exposed to the same amount and regime of shock. After 1 week of training, long-term potentiation (LTP) was measured in vitro in hippocampal slices. Exposure to uncontrollable shock massively impaired LTP relative to exposure to the same amount and regime of controllable shock. These results provide evidence that controllability modulates plasticity at the cellular-neuronal level.