Comparative study by computed radiography, histology, and scanning electron microscopy of the articular cartilage of normal goats and in chronic infection with caprine arthritis-encephalitis virus

In the northeast of Brazil, caprine arthritis-encephalitis (CAE) is one of the key reasons for herd productivity decreasing that result in considerable economic losses. A comparative study was carried out using computed radiography (CR), histological analysis (HA), and scanning electronic microscopy (SEM) of the joints of CAE infected and normal goats. Humerus head surface of positive animals presented reduced joint space, increased bone density, and signs of degenerative joint disease (DJD). The carpal joint presented no morphological alterations in CR in any of the animals studied. Tarsus joint was the most affected, characterized by severe DJD, absence of joint space, increased periarticular soft tissue density, edema, and bone sclerosis. Histological analysis showed chronic tissue lesions, complete loss of the surface zone, absence of proteoglycans in the transition and radial zones and destruction of the cartilage surface in the CAE positive animals. Analysis by SEM showed ulcerated lesions with irregular and folded patterns on the joint surface that distinguished the limits between areas of normal and affected cartilage. The morphological study of the joints of normal and CAE positive goats deepened understanding of the alteration in the tissue bioarchitecture of the most affected joints. The SEM finding sustained previous histological reports, similar to those found for rheumatoid arthritis, suggesting that the goat infected with CAE can be considered as a potential model for research in this area.

Improvement of non-paraneoplastic voltage-gated potassium channel antibody-associated limbic encephalitis without immunosuppressive therapy

We describe a 61-year-old patient with clinical evidence of limbic encephalitis who improved with anticonvulsant treatment only, that is, without the use of immunosuppressive agents. Three years following occurrence of anosmia, increasing memory deficits, and emotional disturbances, he presented with new-onset temporal lobe epilepsy, with antibodies binding to neuronal voltage-gated potassium channels and bitemporal hypometabolism on FDG-PET scan; the MRI scan was normal. This is most likely a case of spontaneous remission, illustrating that immunosuppressive therapy might be suspended in milder courses of limbic encephalitis. It remains open whether treatment with anticonvulsant drugs played an additional beneficiary role through the direct suppression of seizures or, additionally, through indirect immunomodulatory side effects.

Long-term outcome of acute encephalitis of unknown aetiology in adults

Encephalitis is caused by a variety of conditions, including infections of the brain by a wide range of pathogens. A substantial number of cases of encephalitis defy all attempts at identifying a specific cause. Little is known about the long-term prognosis in patients with encephalitis of unknown aetiology, which complicates their management during the acute illness. To learn more about the prognosis of patients with encephalitis of unknown aetiology, patients in whom no aetiology could be identified were examined in a large, single-centre encephalitis cohort. In addition to analysing the clinical data of the acute illness, surviving patients were assessed by telephone interview a minimum of 2 years after the acute illness by applying a standardized test battery. Of the patients with encephalitis who qualified for inclusion (n = 203), 39 patients (19.2%) had encephalitis of unknown aetiology. The case fatality in these patients was 12.8%. Among the survivors, 53% suffered from various neurological sequelae, most often attention and sensory deficits. Among the features at presentation that were associated with adverse outcome were older age, increased C-reactive protein, coma and a high percentage of polymorphonuclear cells in the cerebrospinal fluid. In conclusion, the outcome in an unselected cohort of patients with encephalitis of unknown aetiology was marked by substantial case fatality and by long-term neurological deficits in approximately one-half of the surviving patients. Certain features on admission predicted an unfavourable outcome.

High-throughput procedure for tick surveys of tick-borne encephalitis virus and its application in a national surveillance study in Switzerland

Tick-borne encephalitis (TBE), a viral infection of the central nervous system, is endemic in many Eurasian countries. In Switzerland, TBE risk areas have been characterized by geographic mapping of clinical cases. Since mass vaccination should significantly decrease the number of TBE cases, alternative methods for exposure risk assessment are required. We established a new PCR-based test for the detection of TBE virus (TBEV) in ticks. The protocol involves an automated, high-throughput nucleic acid extraction method (QIAsymphony SP system) and a one-step duplex real-time reverse transcription-PCR (RT-PCR) assay for the detection of European subtype TBEV, including an internal process control. High usability, reproducibility, and equivalent performance for virus concentrations down to 5 x 10(3) viral genome equivalents/microl favor the automated protocol compared to the modified guanidinium thiocyanate-phenol-chloroform extraction procedure. The real-time RT-PCR allows fast, sensitive (limit of detection, 10 RNA copies/microl), and specific (no false-positive test results for other TBEV subtypes, other flaviviruses, or other tick-transmitted pathogens) detection of European subtype TBEV. The new detection method was applied in a national surveillance study, in which 62,343 Ixodes ricinus ticks were screened for the presence of TBE virus. A total of 38 foci of endemicity could be identified, with a mean virus prevalence of 0.46%. The foci do not fully agree with those defined by disease mapping. Therefore, the proposed molecular test procedure constitutes a prerequisite for an appropriate TBE surveillance. Our data are a unique complement of human TBE disease case mapping in Switzerland.

Parameters of Reform and Unification in Modern Japanese Buddhist Thought: Murakami Senshō and Critical Buddhism

Reform is a word that, one might easily say, characterizes more than any other the history and development of Buddhism. Yet, it must also be said that reform movements in East Asian Buddhism have often taken on another goal—harmony or unification; that is, a desire not only to reconstruct a more worthy form of Buddhism, but to simultaneously bring together all existing forms under a single banner, in theory if not in practice. This paper explores some of the tensions between the desire for reform and the quest for harmony in modern Japanese Buddhism thought, by comparing two developments: the late 19th century movement towards ‘New Buddhism’ (shin Bukkyō) as exemplified by Murakami Senshō 村上専精 (1851–1929), and the late 20th century movement known as ‘Critical Buddhism’ (hihan Bukkyō), as found in the works of Matsumoto Shirō 松本史朗 and Hakamaya Noriaki 袴谷憲昭. In all that has been written about Critical Buddhism, in both Japanese and English, very little attention has been paid to the place of the movement within the larger traditions of Japanese Buddhist reform. Here I reconsider Critical Buddhism in relation to the concerns of the previous, much larger trends towards Buddhist reform that emerged almost exactly 100 years previous—the so-called shin Bukkyō or New Buddhism of the late-Meiji era. Shin Bukkyō is a catch-all term that includes the various writings and activities of Inoue Enryō, Shaku Sōen, and Kiyozawa Manshi, as well as the so-called Daijō-hibussetsuron, a broad term used (often critically) to describe Buddhist writers who suggested that Mahāyāna Buddhism is not, in fact, the Buddhism taught by the ‘historical’ Buddha Śākyamuni. Of these, I will make a few general remarks about Daijō-hibusseturon, before turning attention more specifically to the work of Murakami Senshō, in order to flesh out some of the similarities and differences between his attempt to construct a ‘unified Buddhism’ and the work of his late-20th century avatars, the Critical Buddhists. Though a number of their aims and ideas overlap, I argue that there remain fundamental differences with respect to the ultimate purposes of Buddhist reform. This issue hinges on the implications of key terms such as ‘unity’ and ‘harmony’ as well as the way doctrinal history is categorized and understood, but it also relates to issues of ideology and the use and abuse of Buddhist doctrines in 20th-century politics.

The Pursuit of Tangible Happiness: Religion and Politics in a Japanese New, New Religion

The decline of traditional religions in Japan in the past century, and especially since the end of World War Two, has led to an explosion of so-called “new religions” (shin shūkyō 新宗教), many of which have made forays into the political realm. The best known—and most controversial—example of a “political” new religion is Sōka Gakkai 創価学会, a lay Buddhist movement originally associated with the Nichiren sect that in the 1960s gave birth to a new political party, Komeitō 公明党 (lit., Clean Government Party), which in the past several decades has emerged as the third most popular party in Japan (as New Komeitō). Since the 1980s, Japan has also seen the emergence of so-called “new, new religions” (shin shin shūkyō 新新宗教), which tend to be more technologically savvy and less socially concerned (and, in the eyes of critics, more akin to “cults” than the earlier new religions). One new, new religion known as Kōfuku-no-Kagaku 幸福の科学 (lit., Institute for Research in Human Happiness or simply Happy Science), founded in 1986 by Ōkawa Ryūho 大川隆法, has very recently developed its own political party, Kōfuku Jitsugentō 幸福実現党 (The Realization of Happiness Party). This article will analyse the political ideals of Kōfuku Jitsugentō in relation to its religious teachings, in an attempt to situate the movement within the broader tradition of religio-political syncretism in Japan. In particular, it will examine the recent “manifesto” of Kōfuku Jitsugentō in relation to those of New Komeitō and “secular” political parties such as the Liberal Democratic Party (Jimintō 自民党) and the Democratic Party (Minshutō 民主党).

Beyond Belief: Japanese Approaches to the Meaning of Religion

For several centuries, Japanese scholars have argued that their nation’s culture—including its language, religion and ways of thinking—is somehow unique. The darker side of this rhetoric, sometimes known by the English term “Japanism” (nihon-jinron), played no small role in the nationalist fervor of the late-nineteenth and early twentieth centuries. While much of the so-called “ideology of Japanese uniqueness” can be dismissed, in terms of the Japanese approach to “religion,” there may be something to it. This paper highlights some distinctive—if not entirely unique—features of the way religion has been categorized and understood in Japanese tradition, contrasting these with Western (i.e., Abrahamic), and to a lesser extent Indian and Chinese understandings. Particular attention is given to the priority of praxis over belief in the Japanese religious context. Des siècles durant, des chercheurs japonais ont soutenu que leur culture – soit leur langue, leur religion et leurs façons de penser – était en quelque sorte unique. Or, sous son jour le plus sombre, cette rhétorique, parfois désignée du terme de « japonisme » (nihon-jinron), ne fut pas sans jouer un rôle déterminant dans la montée de la ferveur nationaliste à la fin du XIXe siècle, ainsi qu’au début du XXe siècle. Bien que l’on puisse discréditer pour l’essentiel cette soi-disant « idéologie de l’unicité japonaise », la conception nippone de la « religion » constitue, quant à elle, un objet d’analyse des plus utiles et pertinents. Cet article met en évidence quelques caractéristiques, sinon uniques du moins distinctives, de la manière dont la religion a été élaborée et comprise au sein de la tradition japonaise, pour ensuite les constrater avec les conceptions occidentale (abrahamique) et, dans une moindre mesure, indienne et chinoise. Une attention toute particulière est ici accordée à la praxis plutôt qu’à la croyance dans le contexte religieux japonais.

Revisioning a Japanese Spiritual Recovery Through Manga: Kobayashi Yoshinori’s ‘Gōmanism’ as Aesthetics and Ideology

This essay provides a critical analysis of the aesthetic ideology of “Gomanism” in the manga of Kobayashi Yoshinori (b. 1953), particularly Yasukuniron (On Yasukuni, 2005) and Tennōron (On the Emperor, 2009), in order to flesh out the implications of the author’s “revisionist” approach to Japanese religion, politics and history.

Phylogenetic and virulence analysis of tick-borne encephalitis virus field isolates from Switzerland

Tick-borne encephalitis (TBE) is an endemic disease in Switzerland, with about 110-120 reported human cases each year. Endemic areas are found throughout the country. However, the viruses circulating in Switzerland have not been characterized so far. In this study, the complete envelope (E) protein sequences and phylogenetic classification of 72 TBE viruses found in Ixodes ricinus ticks sampled at 39 foci throughout Switzerland were analyzed. All isolates belonged to the European subtype and were highly related (mean pairwise sequence identity of 97.8% at the nucleotide and 99.6% at the amino acid level of the E protein). Sixty-four isolates were characterized in vitro with respect to their plaque phenotype. More than half (57.8%) of isolates produced a mixture of plaques of different sizes, reflecting a heterogeneous population of virus variants. Isolates consistently forming plaques of small size were associated with recently detected endemic foci with no or only sporadic reports of clinical cases. All of six virus isolates investigated in an in vivo mouse model were highly neurovirulent (100% mortality) but exhibited a relatively low level of neuroinvasiveness, with mouse survival rates ranging from 50% to 100%. Therefore, TBE viruses circulating in Switzerland belong to the European subtype and are closely related. In vitro and in vivo surrogates suggest a high proportion of isolates with a relatively low level of virulence, which is in agreement with a hypothesized high proportion of subclinical or mild TBE infections.

Comparison of oral administration of lomustine and prednisolone or prednisolone alone as treatment for granulomatous meningoencephalomyelitis or necrotizing encephalitis in dogs

OBJECTIVE: To compare oral administration of lomustine and prednisolone with oral administration of prednisolone alone as treatment for granulomatous meningoencephalomyelitis (GME) or necrotizing encephalitis (NE) in dogs. DESIGN: Retrospective cohort study. ANIMALS: 25 dogs with GME and 18 dogs with NE (diagnosis confirmed in 8 and 5 dogs, respectively). PROCEDURES: Records of dogs with GME or NE were reviewed for results of initial neurologic assessments and clinicopathologic findings, treatment, follow-up clinicopathologic findings (for lomustine-treated dogs), and survival time. Dogs with GME or NE treated with lomustine and prednisolone were assigned to groups 1 (n = 14) and 3 (10), respectively; those treated with prednisolone alone were assigned to groups 2 (11) and 4 (8), respectively. RESULTS: Prednisolone was administered orally every 12 hours to all dogs. In groups 1 and 3, mean lomustine dosage was 60.3 mg/m(2), PO, every 6 weeks. Median survival times in groups 1 through 4 were 457, 329, 323, and 91 days, respectively (no significant difference between groups 1 and 2 or between groups 3 and 4). Within the initial 12 months of treatment, median prednisolone dosage was reduced in all groups; dosage reduction in group 1 was significantly larger than that in group 2 at 6, 9, and 12 months. Combination treatment most frequently caused leukopenia, but had no significant effect on liver enzyme activities. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with GME and NE, oral administration of lomustine and prednisolone or prednisolone alone had similar efficacy. Inclusion of lomustine in the treatment regimen was generally tolerated well.

Neuropathogenesis of naturally occurring encephalitis caused by Listeria monocytogenes in ruminants

Listeriosis is a serious food-borne disease with increasing frequency in humans and ruminants. Despite the facts that in both hosts, listeriosis can occur as rhombencephalitis and ruminants are a reservoir of Listeria monocytogenes (LM) strains pathogenic for humans, little work has been done on the pathogenesis in ruminants. This study investigates the neuropathogenesis of listeric encephalitis in over 200 natural cases in cattle, sheep and goats by analyzing anatomical distribution, severity, bacterial load and temporal evolution of the lesions. Our results suggest that LM gains access to the brainstem of all three species via axonal migration not only along the trigeminal nerve, but also along other nerves. The ensuing encephalitis does not remain restricted to the brainstem. Rather, LM spreads further from the brainstem into rostral brain regions likely by intracerebral axonal migration. Significant differences in severity of the lesions and bacterial load were found between cattle and small ruminants, which may be caused by species-specific properties of antibacterial immune responses. As histopathological lesions of human rhombencephalitis caused by LM strongly resemble those of ruminants, the disease likely has a similar pathogenesis in both hosts.

Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, "outrunning" the host's immune response in demyelinating plaques, thus continuously eliciting new lesions.

SiRNA inhibits replication of Langat virus, a member of the tick-borne encephalitis virus complex in organotypic rat brain slices

Tick-borne encephalitis virus is the causative agent of tick-borne encephalitis, a potentially fatal neurological infection. Tick-borne encephalitis virus belongs to the family of flaviviruses and is transmitted by infected ticks. Despite the availability of vaccines, approximately 2000-3000 cases of tick-borne encephalitis occur annually in Europe for which no curative therapy is available. The antiviral effects of RNA mediated interference by small interfering RNA (siRNA) was evaluated in cell culture and organotypic hippocampal cultures. Langat virus, a flavivirus highly related to Tick-borne encephalitis virus exhibits low pathogenicity for humans but retains neurovirulence for rodents. Langat virus was used for the establishment of an in vitro model of tick-borne encephalitis. We analyzed the efficacy of 19 siRNA sequences targeting different regions of the Langat genome to inhibit virus replication in the two in vitro systems. The most efficient suppression of virus replication was achieved by siRNA sequences targeting structural genes and the 3' untranslated region. When siRNA was administered to HeLa cells before the infection with Langat virus, a 96.5% reduction of viral RNA and more than 98% reduction of infectious virus particles was observed on day 6 post infection, while treatment after infection decreased the viral replication by more than 98%. In organotypic hippocampal cultures the replication of Langat virus was reduced by 99.7% by siRNA sequence D3. Organotypic hippocampal cultures represent a suitable in vitro model to investigate neuronal infection mechanisms and treatment strategies in a preserved three-dimensional tissue architecture. Our results demonstrate that siRNA is an efficient approach to limit Langat virus replication in vitro.