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Notes: The processing of olfactory inputs by the parahippocampal region has a central role in the organization of memory in mammals. The olfactory input is relayed to the hippocampus via interposed synapses located in the piriform and entorhinal cortices. Whether olfactory afferents directly or indirectly project to other areas of the parahippocampal region beside the entorhinal cortex (EC) is uncertain. We performed an electrophysiological and imaging study of the propagation pattern of the olfactory input carried by the fibres that form the lateral olfactory tract (LOT) into the parahippocampal region of the in vitro isolated guinea pig preparation. Laminar analysis was performed on field potential depth profiles recorded with 16-channel silicon probes at different sites of the insular–parahippocampal cortex. The LOT input induced a large amplitude polysynaptic response in the lateral EC. Following appropriate LOT stimulation, a late response generated by the interposed activation of the hippocampus was observed in the medial EC. LOT stimulation did not induce any local response in area 36 of the perirhinal cortex (PRC), while a small amplitude potential with a delay similar to the lateral EC response was inconsistently observed in PRC area 35. No PRC potentials were observed following the responses evoked by LOT stimulation in either the lateral or the medial EC. These findings were substantiated by current source density analysis of PRC laminar profiles. To further verify the absence of EC-to–PRC field interactions after LOT stimulation, high-resolution optical imaging of neuronal activity was performed after perfusion of the isolated brain with the voltage-sensitive dye RH-795. The optical recordings confirmed that olfactory-induced activity in the EC does not induce massive PRC activation. The present findings suggest that the olfactory input into the parahippocampal region is confined to the entorhinal cortex. The results also imply that, as demonstrated for the PRC-to-EC pathway, the propagation of neuronal activity from the EC to the PRC is hindered, possibly by a powerful inhibitory control generated within the EC.

Notes: In order to examine whether the basal ganglia are involved in arbitrary visuomotor association, we recorded neuronal activity in the internal segment of the globus pallidus (GPi) of monkeys during a conditional visuomotor learning task. Two monkeys were presented a cueing visual stimulus, and following a delay period required to push, pull or turn a manipulator according to the cue. GPi neurons showed changes in activity during the delay period when the animals performed the task on the basis of a familiar stimulus–response association. Those changes in delay activity were enhanced as the monkeys were learning a new visuomotor association. The enhancement of the changes was selective to a following response. These results suggest that the basal ganglia are involved in arbitrary visuomotor association, especially during the learning of new associations.

Notes: Summary Seroepidemiological studies of hemorrhagic fever with renal syndrome (HFRS) virus infection were carried out among urban rats(Rattus norvegicus andRattus rattus) and small field rodents in Hokkaido, Japan. An urban rat colony that was seropositive to SR-11 strain of HFRS virus (laboratory rat origin) was demonstrated in February 1983 at a dumping ground area of Kami-iso Town near Hakodate port. An HFRS-related virus, named KI-262 strain, was isolated from the lung tissue of a seropositive rat using Vero-E6 cell culture. Antigenicity of the isolate was closely related to Hantaan 76–118 and SR-11 strains by the indirect immunofluorescent antibody (IFA) test. No seropositive rat was found among the 861 rats captured in 38 other regions. It is unclear whether or not the infected rats in the positive area were introduced from abroad, though the area is located near Hakodate International Port. Furthermore, higher positive rates of urban rats in the Kami-iso area were observed in the spring and winter than in the summer and fall. Significantly high proportion of positive cases was observed among adult rats (six months or older) than among younger animals. The seasonal and age distribution of postive cases suggested that the virus was not readily transmitted from one infected rat to another. One seropostive case of a small field mouse(Clethrionomys rufocanus bedfordiae) was detected around the Kami-iso area.

Notes: Summary.  Bovine lactoferrin (LF) and ribavirin (Rbv) were tested as antiviral agents against Seoul type hantavirus (SR-11 strain) in vitro. Hantaviral foci number in Vero E6 cells infected with SR-11 was reduced with LF treatment by 5 days post infection to obtain a 50% effective dose (ED50) of 2500 μg/ml, while pretreatment with LF was highly efficacious having an ED50 of 39 μg/ml. Conversely, 1 h pretreatment with Rbv revealed no inhibition of viral focus formation but could significantly reduce the number of viral foci (ED50: 10 μg/ml) when used from the time of viral infection. One hour pre-treatment of the cell monolayer with LF and subsequent addition of Rbv revealed a synergistic anti-hantaviral effect against SR-11, 〈20 FFU/ml as compared to 105 foci/ml in the control. One hour treatment of SR-11 with LF prior to cell inoculation gave an ED50 of 312.5 μg/ml. Whereas, washing the LF-pretreated cell monolayer with PBS demonstrated minimal focus reduction, suggesting LF lightly adheres to cells. These results indicate that LF has anti-hantaviral activity in vitro and inhibition of virus adsorption to cells which play an important role in revealing the anti-hantaviral activity of LF. This paper reports for the first time the anti-hantaviral effect of LF.

Notes: Summary.  To understand the mode of transmission of Seoul type hantavirus in Wistar rats, we examined the shedding of the virus and antibody production in infected rats. When 1-day-old rats were inoculated with KI-83-262 strain of Seoul virus, the S segment of the viral genome was detected in lungs, clots, urine, saliva, submaxillary glands, rectums, and kidneys by nested reverse transcriptase PCR. On the other hand, when 8-week-old rats were infected with the virus, viral genome was detected only in the lungs and rectum. In uninfected newborn rats intranasally administered urine from infected newborn rats, four of six rats shed the virus into their urine. In addition, three of eight rats kept in a same cage with infected animals also shed the virus into urine. Moreover, the virus genome was detected in the urine of urban rats (Rattus norvegicus) in an enzootic focus. These findings suggest that the urine containing virus from infected rats is an actual source of Seoul virus infection.

Notes: Summary.  Ribavirin at concentrations from 1 to 10 μg/ml exihibited inhibitory effects on transcription of Borna disease virus (BDV) in persistently infected cells. Our present study indicates that ribavirin is a candidate anti-BDV drug.

Notes: Summary.  To understand the mode of transmission of Seoul type hantavirus in Wistar rats, we examined the shedding of the virus and antibody production in infected rats. When 1-day-old rats were inoculated with the KI-83-262 strain of Seoul virus, S segment of the viral genome was detected in lungs, clots, urine, saliva, submaxillary glands, rectums, and kidneys by nested reverse transcriptase PCR. On the other hand, when 8-week-old rats were infected with the virus, viral genome was detected only in the lungs and rectum. In newborn rats intranasally administered urine from infected newborn rats, four of six rats shed the virus into their urine. In addition, three of eight rats kept in the same cage with infected animals also shed the virus into urine. Moreover, the virus genome was detected in the urine of urban rats (Rattus norvegicus) in an enzootic focus. These findings suggest that the urine containing virus from infected † rats is an actual source of the Seoul virus infection.

Notes: Summary The cell cycle of fetal lamb kidney (FLK) cultures chronically infected with bovine leukosis virus was synchronized by double thymidine block. The synchronized FLK cells were examined for production of BLV antigen and virion release by cytoplasmic immunofluorescence and syncytia forming assay, respectively. The production of BLV antigens was increased during S and G2 phases and was decreased during M and G1 phases. BLV release was associated with the M phase of FLK cells. Short term lymphocyte cultures from BLV infected cattle were treated with hydroxyurea and mitomycin C. The expression of BLV antigen and DNA synthesis of PHA stimulated lymphocytes was inhibited by both drugs.

Notes: Summary Vector competences ofAedes (Ae.) vexans nipponii (nip.) andCulex (Cx.) tritaeniorhynchus to Getah virus were assessed by using a membrane feeding technique. The Getah virus was present at high titer in both species of mosquitoes after 21 days of extrinsic incubation at 28° C. Infection rates on 21 post-feeding were 100 per cent (4/4) forAe. vexans nip. at a virus dosage of 105.3 PFU/ml and 60 per cent (3/5) forCx. tritaeniorhynchus at similar virus dosage. More than 103.5 PFU of virus was detected in salivary glands of both species of mosquitoes on day 21 of extrinsic incubation. Forty percent (2/5) ofAe. vexans nip. transmitted the virus into serum-agar after ingesting 104.3 PFU/ml of virus blood mixture. In experiments withCx. tritaeniorhynchus ingesting 107.5 PFU/ml of virus blood mixture, 57 per cent (4/7) were able to transmit the virus to suckling mice and 59 per cent (10/17) transmitted the virus into serum-agar.

Notes: Summary.  Regulation of viral RNA levels in infected cells is considered important in the investigation of viral transcription and replication. Amounts of Borna disease virus (BDV) RNAs were increased in confluent persistently BDV-infected MDCK cells (MDCK/BDV) cells, while maintained at low levels in growing cells. The amount of 1.9-kb RNA without cap formation and polyadenylation at the 5′ and 3′ ends respectively were remarkably increased (200% per day) in confluent MDCK/BDV cells. Both the full-length genomic and anti-genomic RNAs were increased accompained by 1.9-kb RNA, suggesting the transcription of the 1.9-kb RNA was important for replication of BDV. Ribavirin has an inhibitory effect on replication and transcription of BDV at concentrations from 1 to 10 μg/ml [Mizutani T et al., Arch Virol (1998)143: 2 039–2 044]. BDV transcripts were decreased with ribavirin treatment and increased after its removal which indicated that ribavirin has a reversible inhibitory effect on BDV transcription. Furthermore, BDV transcription was also decreased by two agents, RMNPA and EICAR, which selectively inhibit enzyme activity related to cap formation at the 5′ end of mRNA. On the contrary, when the growing MDCK/BDV cells were treated with actinomycin D, transcripts of BDV RNA were increased for 24 h. These agents and culture conditions in this study were found to be useful tools for up-and down-regulation of BDV transcription in persistently BDV-infected cells.