Death of a horse infected experimentally with Anaplasma phagocytophilum.

A 19-year-old horse that was one of a group of six horses infected experimentally with Anaplasma phagocytophilum for a study of the pathogenesis of equine granulocytic ehrlichiosis died suddenly two days after first showing clinical signs of disease. The clinical signs and laboratory findings observed before its death were similar to all those of the other infected horses, and to previous reports of this disease. A postmortem examination revealed widespread haemorrhaging in its internal organs, and vasculitis and thrombosis in the kidneys. These changes are consistent with disseminated intravascular coagulation, which has previously been reported in human beings infected with the presumably identical agent of human granulocytic ehrlichiosis.

Cellular composition and interferon-gamma expression of the local inflammatory response in feline infectious peritonitis (FIP).

Feline infectious peritonitis (FIP) is one of the most important viral diseases of cats. International studies estimate that approximately 80% of all purebred cats are infected with the causative agent, feline coronavirus (FCoV). Out of these, 5-12% develop clinical symptoms of FIP. The pathogenesis of the disease is complex with many unresolved issues relating to the role of the immune system. The aim of the present study was to determine the proportions of various inflammatory cell types in FIP lesions by using a panel of cat specific, thoroughly validated, monoclonal antibodies. In addition, the expression of interferon-gamma within the inflammatory lesions was examined by RT-PCR. Our results confirm the mixed nature of the inflammatory reaction in FIP, involving B cells and plasma cells as well as CD4+ and CD8+ T cells. However, one cell type stands out as being the key element in both the "wet" and "dry" forms of FIP: the macrophage. Upregulation of IFN-gamma expression within the inflammatory lesions suggests a local activation of macrophages, which might result in increased viral replication.

Direct effects of corticotropin on plasma lipoprotein metabolism in man--studies in vivo and in vitro.

To explore the roles of corticotropin and corticosteroids in the regulation of plasma lipoprotein concentrations, we investigated the effects of 4 days' administration of corticotropin 1-24 (Synacthen Depot, CIBA-Geigy, Basel, Switzerland) in healthy volunteers and compared them with those occurring during treatment with a synthetic glucocorticoid (dexamethasone). Corticotropin administration resulted in rapid decreases of apolipoprotein (apo) B, low-density lipoprotein (LDL) cholesterol, and plasma triglyceride concentrations of 20% to 30%, whereas dexamethasone treatment did not affect any of the apo B-containing lipoproteins. Lipoprotein (a) [Lp(a)] level was decreased by about 30%; in this case, a similar reduction was noted after dexamethasone treatment. High-density lipoprotein (HDL) concentrations increased with both treatments; however, apo A-I concentrations increased only with glucocorticoid treatment, whereas HDL cholesterol level was elevated after both regimens. The activity of hepatic lipase (HL) was significantly decreased after corticotropin, but not after glucocorticoid treatment. LDL receptor activity, studied in cultured Hep G2 cells, was upregulated by about 30% after incubation with corticotropin. We conclude that corticotropin exerts direct effects on lipoprotein metabolism in man, primarily on apo B-containing lipoproteins, which decrease probably due to a corticotropin-mediated upregulation of LDL receptor activity. The metabolism of Lp (a) seems to be primarily influenced by corticosteroids, which rapidly decrease Lp (a) concentrations. An inhibitory effect of corticotropin on HL activity seems to contribute, besides glucocorticoid effects on apo A-I metabolism, to the increase in HDL level.

Corticotropin-induced reduction of plasma lipoprotein(a) concentrations in healthy individuals and hemodialysis patients: relation to apolipoprotein(a) size polymorphism.

Lipoprotein(a) [Lp(a)], a strong independent cardiovascular risk factor, consists of the unique apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein particle. Apo(a) contains a widely differing number of the plasminogen-like kringle IV, a size polymorphism that is codominantly inherited. In addition to powerful genetic control, renal failure is known to influence the plasma Lp(a) concentration. There is still a lot to be learned about the mode and site of catabolism of Lp(a), and there is no readily applicable Lp(a)-lowering treatment available. Therefore, it was of interest to study further the Lp(a)-lowering effect of corticotropin (ACTH) that has been demonstrated in small studies. The main purpose of the present study was to investigate the influence of ACTH on different apo(a) isoforms. Short-term treatment with ACTH decreased the plasma Lp(a) concentration in all 26 study participants. The two study groups (12 healthy individuals and 14 hemodialysis patients) responded similarly, with a median decrease in plasma Lp(a) of 39% and 49%, respectively. In subjects with two clearly separable apo(a) bands, apo(a) phenotyping and densitometric scanning of the bands before and after treatment with ACTH revealed a change in the proportion of apo(a) isoforms, ie, a shift toward the isoform with lower molecular weight. This was observed in seven of nine investigated subjects (four of five healthy individuals and three of four hemodialysis patients).

Humoral immune response against Borna disease virus (BDV) in experimentally and naturally infected cats.

In order to investigate the peripheral and intracerebral humoral immune response against Borna disease virus (BDV) in cats, serum and cerebrospinal fluid (CSF) samples from experimentally and naturally BDV-infected cats were analysed in two different test systems (indirect enzyme-linked immunosorbent assay and indirect immunofluorescent test). The experimentally infected cats developed high antibody titres against the major immunogenic BDV-proteins, p24 and p40. In contrast, the naturally infected cats showed a comparatively weak humoral immune response. The experimentally infected cats were inoculated with either BDV laboratory strain V or a feline BDV-isolate. Some differences existed between the two groups of cats. The former group developed a higher response against p40, whereas the latter group showed, beside the p40-response, a more pronounced p24-response, similar to the situation in the naturally infected cats.

Peripheral and intracerebral T cell immune response in cats naturally infected with Borna disease virus.

Borna disease virus (BDV) is a neurotropic agent with capacity to cause encephalomyelitis in a wide range of animal species, including horses and cats. Recent studies also point to a link between BDV and human neuropsychiatric disorders. The pathogenesis of Borna disease (BD) has been proposed to be immune-mediated, mainly through the effects of cytotoxic T cells. We used flow cytometric analysis in order to characterize the peripheral and intracerebral T cell immune response in cats naturally infected with BDV. Our results show the presence of two different CD8+ cell populations (CD8+low and CD8+high) in the blood, spleen and brain of these cats. In the brain, CD8+low cells predominated over CD8+high cells. Since CD8+low cells have been suggested to represent a non-MHC-restricted T cell population, the recruitment of such cells to the brains of BDV-infected cats could possibly be of importance for the clearance of virus from neurones.

Ototoxic impact of cisplatin in pediatric oncology patients.

OBJECTIVE: To describe hearing changes in a group of 28 children (age range, 8-180 mo) undergoing protocol-based cisplatin therapy. METHODS: Conventional, play audiometry, visual reinforcement audiometry (VRA), immittance audiometry, transient click evoked otoacoustic emissions (OAEs), and auditory brainstem response (ABR) evoked potentials were used to assess peripheral sensitivity and for threshold determination. RESULTS: Bilateral symmetrical high-frequency sensorineural hearing loss was noted in 9 of the 28 children (26%). Hearing loss was evident as early as 1 month after chemotherapy and as late as 50 months and was not dependent on individual or cumulative dosage of cisplatin. CONCLUSIONS: 1) Presence of sensorineural hearing loss was independent of individual and/or cumulative dosage of cisplatin; 2) audiologic assessment should be incorporated into a child's periodic medical evaluations after chemotherapy treatment, as onset of sensorineural hearing loss cannot be predicted; 3) personal hearing aids may be indicated for those children with hearing loss affecting the low- to mid-frequencies; a personal assistive listening device (frequency modulated system) may be more appropriate for losses above 3000 Hz; and 4) evaluation and intervention by a speech-language pathologist may be indicated to address possible articulation or language development problems consequent to hearing loss.

Pervasive developmental delay in children presenting as possible hearing loss.

OBJECTIVE/HYPOTHESIS: Children who fail to develop adequate language skills and/or appropriate social skills by age 2 years often are referred to the department of otolaryngology for otolaryngologic examination and evaluation of possible hearing deficits. Discovering a gross disparity between hearing function and language ability often uncovers an underlying developmental disorder satisfying criteria for diagnosis on the spectrum of autism and pervasive developmental delay (PDD). The otolaryngologist has a unique opportunity to identify these autistic children and initiate their evaluation and management. STUDY DESIGN: Retrospective review. METHODS: Review of charts of children referred over the past 4 years to the Department of Otolaryngology for possible hearing loss identified 15 children who were later diagnosed with PDD. RESULTS: Fifteen children initially referred for hearing evaluation were subsequently identified with a diagnosis of PDD. Males outnumbered females 4 to 1, with the average age of referral being 2 years. One third of the patients displayed middle ear disease that improved with PE tube placement. One third of the patients showed brainstem conduction dysfunction on auditory brainstem evoked response testing. CONCLUSIONS: Children with developmental delays, especially higher functioning ones, may present with a myriad of language and communication deficits that are often mistakenly attributed to hearing loss. Otolaryngologists and audiologists can assist in their early identification and appropriate referral for therapy.

A variant form of feline Borna disease.

Borna disease virus (BDV) is a neurotropic agent with capacity to infect and cause encephalomyelitis in a wide range of animals, including horses, sheep, cattle and cats. Recent interest in BDV as a potential human pathogen has been stimulated by reports of BDV-specific antibodies and nucleic acid in patients with neuropsychiatric diseases. The pathogenesis of Borna disease (BD) in naturally infected animals is believed to be immune-mediated, mainly through the action of cytotoxic T cells. In this paper, a case of feline BD with atypical clinical and histopathological features is reported. Clinically, the cat showed muscle fasciculation and proprioceptive defects. Despite absence of encephalitis, numerous neurons were infected with BDV as shown by in-situ hybridization. This indicates that BDV infection may lead to various disease patterns, depending on differences in viral pathogenicity, or on as yet unidentified host-specific factors.

Case control study of feline Borna disease in Sweden.

A questionnaire-based, retrospective case-control study of 174 Swedish cats was used to identify possible risk factors for feline Borna disease. The questionnaire consisted of 32 questions on a wide range of subjects, including lifestyle and possible modes of virus transmission. Two control groups were used: a healthy-control and a hospital-control. Variables with significant odds ratios in either the Borna disease:healthy-control or Borna disease:hospital-control comparison were included in multiple logistic regression analyses. Overall, the models suggested that feline Borna disease has a predominantly rural/woodland distribution, that affected cats were more likely to be males than females and intact than neutered, and that they were more likely than not to have hunted mice. The results indicate that, in contrast to other feline viral infections, Borna disease virus is not readily transmitted between cats. The natural reservoir of the virus is unknown. The fact that exposure to mice by hunting was a risk factor for the disease suggests that rodents may be subclinically infected and act as virus carriers.

[The mapping of cortical interaction in the asthenic neurosis syndrome]. / Kartirovanie korkovogo vzaimodeistviia pri sindrome astenicheskogo nevroza.

Topographic mapping method was used to study the spatial-temporal organization of neocortical electrical activity at norm and asthenic neurosis. Patients with asthenic syndrome had shown right hemisphere dominance by the number of cortical interconnections in theta-band and interhemispheric discordance by coherence function.

[Methods of topographic presentation of the bioelectric activity of the brain]. / Metody topograficheskogo predstavleniia bioélektricheskoi aktivnosti mozga.

Prerequisites for developing brain activity topographic mapping and its present status are given. Its advantages and disadvantages, use potentialities in the diagnostic practice of neurological and mental hospitals are discussed.

Detection of herpesvirus DNA in Arctic foxes (Vulpes lagopus; syn. Alopex lagopus) with fatal encephalitis.

A captive breeding programme for the Fennoscandian Arctic fox (Vulpes lagopus; syn. Alopex lagopus) failed due to fatal encephalitis. The aim of this study was to identify the causative agent. Viral nucleic acid was detected by PCR and in situ hybridization in the brain of affected foxes. The results suggest that a herpesvirus might be the causative agent. Whether this infection also occurs in free-living Arctic foxes is unknown.

Neuronal ceroid lipofuscinosis: clinical and morphologic findings in nine affected Polish Owczarek Nizinny (PON) dogs.

OBJECTIVE: The aim of this study was to characterize the clinical and morphologic features of neuronal ceroid lipofuscinosis (NCL) in the Polish Owczarek Nizinny (PON) breed of dog. ANIMALS: Nine Swedish PON dogs of both sexes were included in the study. PROCEDURE: All dogs underwent a detailed clinical evaluation, with emphasis on ophthalmic exams. Histopathology and electron microscopy were performed on the eyes, brain and various internal organs. Immunohistochemical staining for detection of sphingolipid activator proteins (SAPs) and mitochondrial ATP synthase (SCMAS) was performed on the eyes and brain. RESULTS: The dogs showed behavioral abnormalities, motor disturbances and visual impairment or blindness. Pupillary responses were abnormal while fundus changes varied from normal to severe retinal atrophy. Electroretinography (ERG) showed variable changes, from slight alterations in the process of dark adaptation to severely reduced or nonrecordable ERG a- and b-wave amplitudes. Histopathology revealed intracytoplasmic storage bodies within neurons of the brain and in retinal cells, especially the retinal pigment epithelium (RPE). Round to oval granular type of inclusion bodies, known as granular osmiophilic dense deposits (GRODS), were found in neuronal cells in the brain and in the retina. Immunohistochemistry identified the storage material in the brain and retina as consisting of SAPs. CONCLUSION: The presently described NCL disease in PON dogs shows similarities to previously recorded cases in the Miniature Schnauzer. The closest human equivalent to this disease is infantile NCL (CLN1), in which the major stored proteins are SAPs and the ultrastructure of the inclusion bodies of neuronal cells is granular.

Effects of hypoxia and other injurious stimuli on collagen secretion and intracellular growth stimulating activity of bovine aortic smooth muscle cells in culture.

Bovine arterial smooth muscle cells in culture were incubated in hypoxia and total cellular DNA and collagen secretion during and after the hypoxic period was measured as well as the effect of conditioned medium from hypoxic cells on these parameters. Collagen secretion decreased by 16.4% compared to controls during hypoxia but was increased by 41.4% in the post-hypoxic period. Total cellular DNA was significantly lower after both periods. New cultures, receiving conditioned medium from hypoxic cultures, showed an increased collagen secretion by 32.2% compared to controls while total cellular DNA was not changed. Growth stimulating activity, previously shown to be released from lysed cultured SMC, was assayed by exposing SMC cultures to supernatant from lysed cells that had been incubated in hypoxia or exposed to other potential atherogenic stimuli. The growth stimulating activity per cell could be increased by incubating cells in hypoxia, or exposing them to low density lipoproteins or cigarette smoke condensate in concentrations high enough to cause a decrease in cell number. It was suggested that the described effects might contribute to increased cell proliferation and collagen formation in the development of atherosclerosis.