The development of recombinant Adenoviral vaccines to target pneumovirus infection

Respiratory Syncytial Virus (RSV) is a member of the pneumovirus genus (family Paramyxoviridae, subfamily Pneumovirinae). RSV is an important respiratory virus of both infants and the elderly, representing an underappreciated burden on health care systems. In addition, re-infections can occur despite the presence of pre-existing immunity, suggesting that immunological memory to RSV is incomplete. To date, treatment of RSV infection is limited to the provision of supportive care and no effective vaccine is available. Although several are currently under investigation, these candidates focus upon the delivery of the F and G antigens of RSV to stimulate the immune system, rather than the internal antigens, which may provide cross protection between different subtypes of RSV. Vaccine development has been greatly hindered by the lack of an appropriate animal model in which to study vaccine efficacy and pneumovirus pathogenesis. Pneumonia virus of mice (PVM) is also a member of the Pneumovirus genus and, like RSV infection of humans, causes a bronchiolitis and fatal pneumonia in its natural host, the mouse. PVM has been proposed as an appropriate model system in which to both study pneumovirus pathogenesis and vaccine efficacy. The PVM model system was adapted to investigate a potential vaccination strategy to address the lack of an available RSV vaccine. Replication deficient recombinant adenovirus serotype 5 (rAd5) vectors were constructed which expressed the F, M and N genes of PVM J3666, in addition to a control construct, which expressed the LacZ gene of E. coli. The constructs were administered via the intranasal route to BALB/c mice and were able to elicit complete protection against a lethal dose of pathogenic PVM J3666, in both short-term experiments and in a long-term experiment, up to 20 weeks post immunisation. The protection effect elicited by the constructs was observed when administered in a single dose, and in alternative mouse strains, C3H/He-mg and C57BL/6, which had differing immunity haplotypes. The rAd5 vectors generated a PVM specific IgG humoral response to PVM and Ad5 antigen which did not correlate as the primary mediator of protection. The rAd5 candidate expressing the N gene of PVM was shown to induce IFNγ secreting T-cells. The use of a peptide library of PVM N protein determined that a specific response could be identified towards the amino acids N41-90, N81-130, N161-210 and N281-330. Thus, the PVM infection model of BALB/c mice provides an immunological platform to facilitate the study of RSV and PVM pathogenesis, immunology and vaccine development.EThOS - Electronic Theses Online ServiceMedical Research Council (Great Britain) (MRC)GBUnited Kingdo

Follistatin-like 5 is expressed in restricted areas of the adult mouse brain: Implications for its function in the olfactory system

Follistatin‐like 5 (Fstl5), a member of the follistatin family of genes, encodes a secretory glycoprotein. Previous studies revealed that other members of this family including Fstl1 and Fstl3 play an essential role in development, homeostasis, and congenital disorders. However, the in vivo function of Fstl5 is poorly understood. To gain insight into the function of Fstl5 in the mouse central nervous system, we examined the Fstl5 expression pattern in the adult mouse brain. The results of in situ hybridization analysis showed a highly restricted pattern of Fstl5, namely, with localization in the olfactory system, hippocampal CA3 area and granular cell layer of the cerebellum. Restricted expression in the olfactory system suggests a possible role for Fstl5 in maintaining odor perception

運転時の速度評価

The present study was intended for investigating some factors of the traffic accident. The major part of the accident arose from the driver\u27s carelessness. On the factor of the traffic accident, following two factors were in the top level : against the safety speed and the driving under the influence of wine. The speed control in the driving is operated by the speed indicator. Therefore, it is impossible to watch the speed indicator carefully and repeatedly. During the driving, the driver should watch on the road, at the signals, pedesstrains and other motor vehicles. Then, the speed-feeling which obtained by the past experience was examined. The speed-feeling would be depended on the compound sensation including the visual, the acoustic sensation, the sense of the equilibrum, the sense of the movement and the autneus sensation. The three points were examined : (1) Dial operation, (2) Oral estimation and (3) with eye bandage estimation. Following results were obtained : 1. The error extent in the speed-estimation was + or - 10km/h. 2. The over and under-estimate was depended on the initial speed. 3. The velocity appreciation was influenced by the visual factor. 4. The speed-feeling was influenced by some sensations besides the visual sensation. And it was seemed that the sense of the acceleration in the labyrinth would not be disregared

学生の健康状態の経年推移に関する研究(第1報) : Cornell Medical Index (CMI)健康調査の結果

Among 231 new students--in the class of 1982, 205 male, 26 female students-- this research was conducted on 174 male and 19 female students, who took the CMI-Health Questionnaire three times continuously in \u2782, \u2783 and \u2784, in order to reveal the transition and the features of the health condition of a group. The final purpose of this research is to collect basic data for making the college original list of the health questionnaire. The studied matter and obtained information are as follows: 1. The Complaint Rate by Small Categories. The high Complaint rate in small-categories were "anger", "habit", "eye and ear", "respiratory organ" and "fatigue" etc., and this tendency was the same as that of other universities. Concerning the longitudinal transition, almost no difference was seen in each physical small-categories, while in the mental ones, the complaint rates tended to become lower with each year that went by. 2. The Distribution of the All Items, the Physical Category and the Mental Category. Each distribution showed a large inclination to the left, which suggested that it was necessary for us to be wary of analyzing the statistics in establishing the screening level. 3. The Longitudinal Transition of the Complaint Rate in the All Items, the Physical Category and the Mental Category The complaint rates in the physical category were shifted almost at the same level, while in the mental category, they tended to become lower every year. 4. The Judgment Result of the Neurotic Tendency by FUKAMACHI\u27 method. The apperance rate of our college students who had the neurotic trend or of those who were suspected to have it was lower than that of other universities and tended to become lower every year. Notes; In this report, "item" meams questionary, "small-category" means physical organs from A to L and mental characteristic from M to R. And "physical category" includes all physical small-categories and "mental category" includes all mental small-categorys. And "all items" includes both physical and mental categories

スポーツ選手の時間評価(I)

The purpose of this study is to make the exactness of the time estimation of sportsmen experimentally clear. Subjects are 35 male students in Sendai College, including sprinters (100m, 400m), middle-long distance racers, jumpers, throwers, volleyball and tennis players. They were asked to estimate exact times on nine time conditions of 10", 11", 12", 50", 55", 60", 90", 120", and 150", by using a digital stop watch. The main findings are as follows: In general, as subjects repeat trials, the time estimation of subjects tends to approach to exact times. As tennis players repeat trial times, their time estimation is over than that of other players. It does not always follow that the time estimation of track athletes is more exact than that of other players

スポーツ選手の時間評価(II)

The purpose of this study is to clarify the effect of various physical conditions on time estimation and to estimate the time required 150m. and 250m. distance runs. Subjects were 16 male students in Sendai College, including long distance runners, throwers, sprinters, jumpers and the group as a control was consisted of 15 male students including the players of Judo, Kendo, Vollyball, Soccer, Gymnastics and Basketball. Experiment 1 Subjects were asked to estimate the exact time of 30" in rest and after 5 minutes\u27 exercise. Experiment 2 Subjects were asked to estimate the time required 150m. and 250m. distance run. The main findings were as follows: 1-1 Both groups had a tendency of over estimation in rest. 1-2 The time estimation after exercise, sprinters had a tendency of under estimation. Long distance runners, throwers, jumpers and control group had a tendency of over estimation. 1-3 There was significant difference between time estimation in rest and that after exercise. 2-1 In the time estimation of 150 m. distance run, both experimental group and control group had a tendency of under estimation. There was little difference in the time estimation between groups. 2-2 In the time estimation of 250 m. distance run, both groups had a tendency of under estimation. The longer the distance was, the more variable the time estimation was. Results are discussed in terms of intermediating factors