TPC NEWS

TPC NEWS, Vol. 11, No.2, Fall, 1992 (Whole Number 20)

(English Summary)

Page-3 Message from the chief director of the Corporation for Production and Research of Laboratory Primate (CPLP)

Page-4 Farewell message from the former chief director of CPLP

The Tsukuba Primate Center for Medical Science (TPC), the branch of the National Institute of Health in Japan has operated in partnership with the Corporation for Production and Research of Laboratory Primates (CPLP). In this May, the chief director of CPLP changed from Dr. K. Kanemitsu to Dr. T. Matsuura.

On Page 3, Dr. Matsuura gives an inaugural greeting, expressing his hope and decision as the new chief director. On Page 4, Dr. Kanemitsu presents a farewell message. He expresses his appreciation for the cooperation of many people during his term of service and expectation for the future of CPLP.

Page-5 Study, Inspiration, and chaos

A couple of years ago, I saw an impressive presentation in a symposium on "Developing basic technology for understanding the brain function," which was held by a research group supported by the Science and Technology Agency. The presentation was a video of a robot learning how to walk fast. Though I said "Robot," it was simple in shape just like a compass used for drawing a circle.

Well, the compass-like robot lying on a desk began rolling, as it sometimes twitched its "ankles" and "knees." The movement of rolling changed to creeping and then to inchworm-like movement. Suddenly, at the peak of inchworm-like movement, the legs bent upward, and the robot hopped around. After that, the robot finally dashed out like a 100-meter sprinter. All of the audiences burst out laughing, because the compass on the display looked just like a human. However, a professor of technology explained that only a few lines of program, which involved one command such as "Adopt a gain in a new movement." was enough for developing all these diverse movements. I was very surprised that only one command had resulted in such a lot of free-patterns.

Neural circuits are so complicated that the mechanism of information processing, memory, and studying is one of the main themes. The resolution of these themes will not come until the 21st century. A parallel processing neuro-computer is under development right now. However, it is interesting that very simple program can make a motivation for studying behavioral patterns.

There is a hypothesis explaining the importance of lateral thinking: neural circuits are so conservative that it is very difficult to free our thinking from them once established. It is recommended that we switch our vertical thinking to lateral thinking to get inspiration. A similar example is also seen in an explanation on how to use effectively the right brain and left brain.

Back to the movements of the compass-like robot. Here the inchworm-like movement suddenly changed to hopping. The key point is that the change seemed to be on the extension line of the inchworm-like movement, but the change happened discontinuously, that is, the peak of the movement have suddenly converted to an entirely different movement. I find something here that is in common with

inspiration. Although inspiration can not be derived without studying, it looks as if it belongs to a different category than studying and it does not seem to be anextension of studying. I think this is the reason that the books on how to get inspiration or know-how on thinking are very popular.

Recently, chaos theory has become a topic in the fields of physics and

mathematics. Some people say that it is the biggest discovery in the 20th century. This discovery explains from the view point of non-alignment how the chaos condition, that is, sway, turbulence, irregularity, etc., occurs. Irregularity seen in our surroundings has been said to be unpredictable, because it involves too many factors. However, chaos theory revealed that when more than three factors work in a system, the resulting motion becomes chaos according to its determinism, that, therefore, the chaos condition can be easily derived from very simple factors.

As for the turbulence in a world of chaos, a motion (a locus of solutions by mathematics) behaves as if it suddenly becomes a different motion. For example, the swing of a pendulum suddenly converts to a circular motion as the swing grows, and the patterns in water out of the faucet or a river suddenly change shape as the flow speed changes. In chaos theory, discontinuity, irregularity,and unpredictability are not regarded as opposite concepts to continuity, because it involves in continuous changes.

A kind of discontinuity is seen in the process of studying. It seems to be suchan unpredictable matter like inspiration. But in the chaos world in the brain, the discontinuity and unpredictability may be regarded as continuity. In this meaning, only one thing, to enlarge the swing, is needed to convert the swinging motion to acircular motion. Therefore, to swing continuously like a pendulum, that is, to think deeply in ones mind continuously about a theme, is indispensable in getting inspiration.

Page-6 The Ministry of Health and Welfare starts the program "Use of primates in biomedical research for longevity"

The research groups on the program "Use of primates in biomedical research for longevity" started their activities in April this year, being supported by a fund of The Ministry of Health and Welfare. Three themes are to be studied in the following three years.

1). Development of the animal model of nonhuman primate for the research on longevity:

Survey on the influence of aging on the onset of metabolic and senile diseases such as diabetes, hyperlipemia, retinal degeneration, and osteoporosis.

Developing the animal model of dementia by using slow viruses.

Survey on the pedigree which frequently suffers from diseases to specify the high-risk group and identify the risk factor on the onset of senile diseases. Analyzing the genes related senile diseases, and establishing high-risk families.

2). Establishment of information network on laboratory animals in the research on

longevity:

Collection of information on laboratory animals in the research on longevity, and development of a database. Information should be open to public, and the system to access through PC on line network and connect databases in and out of Japan should be established.

Establishment of the information network on genes related senile disease in laboratory animals corresponding to the human Genome project.

3). Establishment of the techniques of rearing management on aging monkeys and training for animal technician:

Compiling the techniques of rearing management accumulated so far, and a training manual should be made.

Page-7 Survey on antibody against Tsukuba Simian Varicella-like Herpesvirus (TSVH) in the colony of cynomolgus monkeys

T. Narita, R. Mukai, and M. Takasaka

We have reported previously on the prevalence of exanthematous disease in our cynomolgus monkey breeding colony from 1989 to 1990, caused by Tsukuba simian varicella-like herpesvirus (TSVH), (TPC NEWS, vol. 9, No. 2, 1990). We present here the serological status of the affected monkeys at one year after the end of the epidemic. All animals in our cynomolgus monkey colony were surveyed to know the sero-converted individuals during this period. Together with immunofluorescent assay (IFA), we used the neutralized antibody test (NT), which we have established, and DOT western blotting EIA (DIA) for detecting the antibody against TSVH.

1. Screening of the antibody against TSVH in cynomolgus monkey breeding colony one year after the end of the epidemic.

The results of serological survey on the antibody to TSVH are shown in Table 1. Numbers indicate all the monkeys tested in Building No.1. The number of sero-positive animals in Room 2, from where the first case of TSVH infection appeared, was 35 out of 101 animals, at the end of the epidemic (June, 1990).

Sixteen animals out of 35 positive ones were removed from this room later, and 19 remainders were still positive to TSVH except one animal at one year after the end of the epidemic (Oct. to Dec. 1991). This animal was negatively sero-converted (<1:10,IFA). To this Room 2, 37 laboratory-bred monkeys were introduced after the end of the epidemic, resulting the total number of animals 132. The serological test in 1991 revealed 3 additional sero-positive monkeys. One out of the 3 newly sero-converted animals was due to the maternal antibodies, and the other two were infected without any clinical signs after the end of the epidemic. Because, the second one became sero-positive between June and Oct. 1990, and the third one sero-converted between Oct. 1990 and Oct. 1991.

As for Room 3, 3 out of 55 positive ones were negatively sero-converted in 1991, 2 of which were due to the maternal antibodies. In Room 5, in which the animals are exceptionally group caged, there were 12 positive (1:10, IFA) animals at the end of the epidemic, but the survey on the remainders (7 animals) in Dec. 1991 revealed that all the animals in this room were negatively sero-converted (<1:10, IFA). Testing the sera from these IFA positive animals by DIA method demonstrated that these were negative to TSVH (<1:10, DIA). To reconcile the discrepancy of the results between IFA and DIA, we estimated that false positive data by IFA may be resulted by the cross-reactivity of the antibodies against other herpesvirus such as CMV or EBV. The results of the serological test on the monkeys in Buildings No.2 and No.3 are shown in Table 2. One sero-positive monkey in Building No.3 was transferred from other laboratory of NIH Japan long time ago, and IFA titers of this monkey were 1:160 (1979) and 1:20 (1990 and 1992).

2. Estimation of the source of the epidemic by TSVH infection

Our serological survey on TSVH revealed that several monkeys in our colony had been sero-positive for TSVH before their arrival at TPC. One of such monkeys (Taro, See, Cover of this issues.) was kept in Room 2, where the onset of this epidemic occurred. There was no other sero-positive monkey in this room. IFA titers of Taro's sera, one year and 4 months before, and 3 months before the onset of the epidemic, were 1:10 and 1:40, respectively. And no neutralizing antibodies were detected in both periods. However, Taro was also infected in the middle of the epidemic, giving rise to the neutralizing antibodies in his convalescent sera. We concluded that this monkey was the source of the infection of the first case animal whose cage was located in front of the Taro's in Nov. 1989.

Page-9 Detection of B virus related antibodies by enzyme-linked immuno sorbent assay (ELIZA) using HSV-1 antigen

Kohji Fujimoto

This report discusses the efficiency of ELIZA using purified HSV-1 antigen for monitoring B virus infection in the monkeys colony.

Antibodies to Herpesvirus simiae (B virus) in cynomolgus monkey sera were detected by ELIZA using purified herpes simplex virus 1 (HSV-1) antigen that is sharing the same antigenicity with B virus. IgG antibody to HSV-1 was detected by the indirect method shown in Figure 1. Purified HSV-1 virion protein was fixed to a plate and diluted monkey serum was reacted with it, and then alkaline phosphatase conjugated anti-cynomolgus monkeys IgG antibody was added and allowed to react with the substrate. Final antibody titer was expressed as the highest dilution of serum in which the absorbance value in the well coated with virus antigen is more by 0.2 than in the well with normal cell antigen (arrow in Figure 2).

Good correlation was obtained between antibody titers to purified HSV-1 antigen and those to crude B virus antigen (Figure 3). This ELIZA could detect antibodies in some monkeys in which the antibodies were not detected by our routine compliment fixation test (CF) using HSV-1 antigen (Figure 4).

Age-related antibody prevalence to HSV-1 in F1 cynomolgus monkeys born in TPC is presented in Figure 5. After disappearance of maternal antibodies after four months of age, no antibody to HSV-1 was detected till five years of age. A few laboratory-bred monkeys had antibodies after six years of age, because they were unusually mated with antibody-positive wild-originated monkeys. These results indicate that our breeding and rearing systems are effective to prevent B virus infection from mother to infant or infant to infant.

Since IgM is produced in the early phase of infection, detection of IgM antibody to a virus is important to know whether the infection recently occurred or not. IgM antibody to HSV-1 in cynomolgus monkey sera was detected by double antibody sandwich ELIZA as indicated in Figure 6. IgM antibody to HSV-1 was detected in the laboratory-bred female monkeys mated with the wild-originated male monkeys which had had antibody to HSV-1.

Page-12 The scope of TPC's tasks has been expanded

The Tsukuba Primate Center for Medical Science (TPC) reorganized its task and renewed the name of divisions.

Division of Disease Control

Quarantine and health checks of nonhuman primates for medical science, studies on health control of laboratory primates, and developing animal disease models.

Division of Breeding and Rearing

Breeding, rearing, and supplying laboratory nonhuman primates, as well as gene conservation and distribution of information on laboratory primates.

Page-13 Purulent myelitis in an aged cynomolgus monkey

Ippei Sakakibara

There are many reported cases of the abscess which primarily develops at the site of a bite and metastasizes to other internal organs. The case, we report here, is an extremely rare case of purulent myelitis caused by metastasis from the abscess of skeletal muscle.

Case: A 22 years old, female, cynomolgus monkey housed individually in a stainless steel cage. By magnetic resonance imaging (MRI), she was found to have an abscess (1 cm x 4 cm) on the right side of the lumbar muscle. Three days before her death, we noticed the following symptoms: anorexia, ataxia, and dyserthesia of the hind leg. She fell into a moribund state and was euthanized.

Pathological findings: When the skin was flayed a large amount of pus exudated from the abscess, which was consisted of two parts being connected by a fistula. The abscess was located in the muscle between segment L4 and L6 of the spinal cord. The pus was mucoid, half transparent and slightly reddish in color. Staphylococcus aureus was isolated from the abscess, spleen, and the adrenal gland.

Histological findings: As shown in Fig. 2, the infection reached directly the vertebral canal from the suppurative lesion along the nerve fiber. Inflammatory exudate was in the vertebral canal. Extensive disruption of the myelinated fibers was observed in the lateral white matter segment L4 of the spinal cord (Fig. 3). A small number of polymorphs nuclear cells infiltrating into the gray matter adjoining the lesion were found. A Gram-staining positive bacillus, a suspected causative agent, was found on the degenerated nerve fiber nearby the disrupted lesion in the vertebral canal.

Page-14 Clinography: prologue

Fumiko Ochikubo

Four months have passed since I got a position as a clinical veterinarian at the Corporation for Production and Research of Laboratory Primates (CPLP). I investigated Canine distemper virus (CDV) -induced encephalitis in squirrel monkeys at the Institute of Medical Science of Tokyo University before I started working at TPC.

Squirrel monkeys with CDV-induced encephalitis showed characteristic clinical signs such as seizure or myoclonus, and had abnormal EEGs such as periodic synchronized discharge (PSD). Histopathologically, there were gliosis and neuronal degeneration diffusing in both the gray and white matters at the subacute phase, and the lesions resembled to those found in acute viral encephalitis and subacute sclerosing panencephalitis (SSPE) in children. Auditory brain stem response (ABR) changes were remarkable at the subacute phase, and the recovery of the latency peak of ABR correlated with survival time. Visual evoked potential (VEP) disappeared at the acute phase and appeared again with the delayed latency peak of VEP at the subacute stage. One monkey did not show any neurological signs, but had the pathological changes with VEP abnormalities. These data suggest that the evoked potentials such as ABR and VEP are helpful in judging the prognosis, and that these squirrel monkey models are useful for the analysis of the pathogenesis of viral encephalitis.

I now do clinical veterinary work on the non-human primates housed at TPC. One of the main problems of primate veterinary work is that the monkeys, in spite of their probable sickness, do not wish to reveal their weakness. Therefore sometimes they die without any treatment. If we can find a way of observing them so that we can notice any weakness of them, then we could make their environment more comfortable. The provision of veterinary medicine for monkeys' well being is as important as the biomedical research work.

Page-15 A plan for a stable supply of nonhuman primates for biomedical research

Yasuhiro Yoshikawa, Fumiaki Cho, Michihiro Suzuki, and Hiromi Ohto. 1. Analysis of dynamic equilibrium

Purpose

TPC breeds nonhuman primates by self-sustaining production system. During 14 years after the establishment of TPC, the proportion of wild-originated monkeys (Fo) to all breeders has become less than 10%, and laboratory-bred monkeys (F1 or more) have become main breeders. The data on the laboratory-bred monkeys have accumulated enough to make a simulation of a stable supply. Therefore we try in this paper to know the colony size that can produce stable supply of nonhuman primates for biomedical research.

Method

We had to establish by ourselves the methodology for this analysis through trial and error, because there was no other example of large-scale, indoor, self-sustaining breeding system in the world but TPC.

Factors were derived from the data on the laboratory-bred monkeys. No data on the wild-originated monkeys were used. Each factor was calculated by using the data obtained from the breeding methods which would be continuously adopted hereafter.Since fluctuation of the number of breeders by years causes difficulty in figuring out the colony size for stable supply of monkeys, we imaged a dynamic equilibrium and figured out the size (Fig. 1).

Results

A. Factors

1) Age of primiparas

Mating pattern gave no significant difference to the age of primiparas (Table1). At the present moment, the age of five years and seven months was regarded as the average age of primiparas. On the other hand, the distribution of the age of all primiparas born after 1980 showed that 70% of them were four, five and six years old (Fig. 2). Therefore, four, five and six years old monkeys were regarded as primiparas and those that were seven or more years old as multiparas. Because primiparas and multiparas are different in various parameters, we categorized the monkeys like this.

2) Rate of normal birth

Tables 2a and 2b show the rate of normal birth. The rate of normal birth of the primiparas was 83.3%, and that of the multiparas was 89.9%.

3) Number of birth per year

It was difficult to decide the number of birth per year, because the actual colony had no mathematical equality. Therefore, we figured out the number of birth per year on an assumption that the dynamic equilibrium was established at a certain moment: that is, we surveyed that at a random point of the time what breeding-stages were consisted in each age of breeders. Table 3a shows the number of the animals of four breeding stages from 1987 to the end of May, 1991.

To revise the deviation derived from the months surveyed, we investigated the rate of pregnant animals of every three month of each age. Table 3b shows that the average rate of every three months was 10.1% with the primiparas, and 16.2% with the multiparas. The confidence interval was 7.5% - 12.7% with the primiparas, and 15.4% - 17.0% with the multiparas. Since these figures were used as the base of estimated values which we would describe later, all values are considered to have 25% (2.6/10.1) deviation with the primiparas, and 5% (0.8/16.2) with the multiparas.

The mean value of E₁ (pregnant) of the five and six years old animals was 0.101, and that of the seven and more years old was 0.162. The number of birth per year was figured out by calculating how many female breeders became from E₁ to E₂(nursing). Pregnancy was confirmed by using an ultra-sonic apparatus 35 days on average after the female breeders became pregnant. An average pregnancy period of the cynomolgus monkey is 165 days. Hence, all females of E₁ group are considered to transfer to E₂ group after 130 (165 - 35 = 130) days.

When the group of female breeders is express by A, the number of birth .

365

per year is A x E₁ x ___

130 .

Fig. 3 is the outline of calculating the number of animals of normal births in the colony of dynamic equilibrium. The proportion of primiparas to all female breeders (A) was 3/12, and that of multiparas was 9/12.

Consequently, the number of births per year with the primiparas was

3 365

A x ___ x Primiparas' E₁ x ____

12 130 .

And referring to Table 2a, the number of the normal birth with the primiparas was

The number of birth x 0.833.

Similarly, the number of normal births with the multiparas was

9 365

A x ___ x Multiparas' E₁ x ______ x 0.899

12 130

Accordingly, the total number of normal birth per year was represented as

follows: A x 0.059 + A x 0.307 = 0.366A.

4) Total number of breeders

TPC's colony consists of males and females at the ratio of 1 to 10. When the number of female breeders is represented by A, the apparent total number of breeders (B') is

B' = A x ___

10.

Table 4 shows the death rate (T) in the breeding colony. It is needed to supplement

the number of deaths with new breeders to maintain the colony. Therefore, the real

total number of breeders (B) was calculated by the following formula:

B = A x ___ x ( 1 + T ) = A x 1.10.

Hence, the number of the animals which have to be introduced to the group of breeders every year (Y) became

B A x 1.11

Y = ___ + B x T = __________ + A x 1.11 x T = 0.102A.

12 12

5) Rate of successful weaning

Laboratory-bred monkeys have more problem in nursing than wild-originated monkeys. In particular, the rate of successful nursing of the laboratory-bred primiparas is low (67%), and that of multiparas is 91%. Therefore we have adopted foster or artificial nursing to rise up the rate of successful weaning.

The number of weanlings with the primiparas was

A x 0.059 x 0.847 = 0.050A.

And, the number of weanlings with the multiparas was

A x 0.307 x 0.92 = 0.282A.

Hence, the number of weanlings per year was

0.050A + 0.282A = 0.332A.

6) Rate of successful rearing

Table 6 shows the number and the rate of survivals three years after birth. No animals supplied for the vaccine safety test were involved in the data. There was no difference between the survival rate of primiparas' weanlings and that of multiparas' (91.7%). As the period of weaning is 5 - 6 months, 8.3% of the animals decreased for 2.5 years. Therefore, decrease per year was 3.32%. Consequently, the total number of animals of two years old was

A x 0.332 x 0.950 = 0.315A.

B. Colony size

Fig. 4 shows the colony size based on the dynamic equilibrium applied the factors mentioned before. The number of animals supplied to vaccine safety tests (a) becomes theoretically as follows:

a = 0.315A - 0.102A = 0.213A.

The numbers of animals according to age are:

0 - 1 years old ---- 0.332A

1 - 2 years old ---- 0.321A

2 - 3 years old ---- 0.255A

3 - 4 years old ---- 0.153A.

Since the total number of breeders is 1.110A, consequently, colony size (S) is 2.171A.

Discussion

Fig. 4 means that a group of 1,110 breeders (1,000 females, 100 males for mating, and 10 animals for supplement) produces 366 normal birth for a year, of which 322 animals weans successfully and 315 animals survive until the age of two years. It is needed introducing every year 102 animals (92 females and 10 males) into the group of breeders. In this case, the colony size is 2171 animals, and 213 animals can be supplied. Since 315 survivals would consist of about 157 females and males,147 males and 66 females would be supplied. This shows that self-sustaining supply is possible theoretically.

The colony size (S) and the number of animals supplied (a) are expressed by a simple equation, S = 10.19a. If the number of the animals supplied is 100, the colony size becomes 1019, accordingly. The NIH of Japan needs 150 monkeys per year for vaccine safety tests. In this case the colony size is

150 x 10.9 = 1529.

In addition to this number, 30 animals at the lowest are needed for virulence tests.

The colony size in this case is

180 x 10.9 = 1834.

Also in the future, we will have to go on breeding monkeys by trial and error, revising the breeding system on the basis of our new data. Each factor ischangeable, accordingly. For example, the rotation line breeding system should be modified to decrease the number of the animals taking a rest (E3), and females should be introduce into the breeding group from the age of 3.5 and should have been selected as candidates for breeders by the age of 6. Table 7 shows the figures of this ideal case. The number of normal birth per year with multiparas is

9 365

A x ___ x 0.23 x ______ x 0.899 = 0.435A.

12 130

The number of normal birth per year with primiparas is 0.059A. Hence the sum of normal birth per year is 0.059A + 0.435A = 0.494A.

Fig. 5 is the dynamic equilibrium on the basis of the data of ideal mating plan. The number of the animals supplied is a = a1 + a2 = 0.329A. Colony size is S = 2.869A. Therefore, S = 8.72a. Fig. 6 shows the colony size on the basis of the ideal mating plan.

The number of animals supplied, 30 per year, seems to be small; but experimentation on monkeys usually is done for three to five years, investigating longitudinally one animal. For example, when one experiment needs four years on average, 30 x 4 = 120 animals can be supplied. Therefore we can offer stable supply of monkeys to six research facilities using a unit of 20 monkeys.

Finally, this plan for a stable supply is much different from the present condition of TPC, in which breeders' age gathers around 9 to 11. It is an important subject how we make this state transfer to the dynamic equilibrium, and how we establish the formula to evaluate the quality of breeders.

Page-20 A program from the present condition to the dynamic equilibrium

Yasuhiro Yoshikawa and Keiji Terao

In this note, we discuss a program to transferring the present condition to the dynamic equilibrium by which we can supply 150 monkeys per year.

Fig. 7a shows the present condition of the female breeders. We will be able to obtain stable number of normal births for several years until the present breeders retire. The reason why the numbers of the breeder candidate of three to seven years are small, is that groups of candidates were supplied for safety tests in spite of the fact that in those days the present breeders had been primiparas with low normal birth and weaning rates. Moreover, we experienced an epidemic of Tsukuba simian varicella-like herpesvirus (TSVH) in 1989, which caused the death of breeders and decrease of the number of one-year-old animals.

If all female monkeys except the animals to be supplied for safety tests were involved in the group of breeders from now, the lowest portion of Fig. 7a would become the main breeder by 1999 after the present breeders would have retired. This situation would imply a supply crisis. However, it would gradually recover by 2006 to the dynamic equilibrium that could supply 150 animals (Fig. 7d). The changes of these process are shown in Figs 8a and 8b.

On the other hand, if we take a system of 1200 animals because of budget limitation and go on supplying 150 animals, introducing new breeders will become impossible in three years (Figs 9a and 9b). This means the collapse of the group of breeders in 10 years. Then we can not stop collapse even if we try to make it recover.

It is critical for the stable supply of 150 animals per year that the difference of about 300 animals, the remainder, from the number of the equilibrium, 150 x 10.19 = 1529.

Page 22 Psycho-ethological characteristics in aged monkeys

Takamasa Koyama

We are conducting two types of psycho-ethological research to investigate whether the behavior of aged M. fascicularis is available for human aging model. The first is to score the aged monkeys' curiosity which seems to be the overall reflection of their neuro-cerebral dysfunction. The second is to study their immuno-ethological responses in a couple of stress induced situations.

(1) Responses of aged monkeys to novel stimuli

It has been reported that human adults lose curiosity to novelty and narrow their ranges of interests as they grow older. We investigated the changes of curiosity in aged (over 20 years old) and young (4 years old) female monkeys. We made a computerized WGTA-like apparatus to examine the responses of 8 aged and 8 young monkeys to novel stimuli presented on a computer display. We also observed their behaviors during training. The aged monkeys frequently showed exploratory behavior, but they did not successfully complete the training task. The important factor for a correct response may be an effective behavioral transfer to handling a computer display monitor, but more research is necessary to support this hypotheses. Since the touch screen was

not very sensitive, the subjects were required to push the screen rather than just to touch it. The amount of force necessary for the response to be recorded might have made the task more difficult for the aged monkeys. In a sense, the score of the aged monkeys might have not necessarily shown actual strength of their curiosity. We have improved the apparatus with a more sophisticated and sensitive touch screen to solve this problem.

(2) Responses of aged monkeys to the social stress

Experimental studies are inevitable to see general organic self-defense mechanisms of the aged people who are exposed to several kinds of psychologically stressful situations. Since experiences of strong physical stress like dropping into the water are uncommon in our daily life, we put aged monkeys into more common and milder psychological stress such as housing with unfamiliar young monkeys. After 2-week together housing, we compared their behavioral responses to those of the young monkeys.

The aged monkeys did not show any clear physiological responses when they were exposed to social stress. But from another experiment, we knew that the aged monkeys increased serum cortisol when they were socially isolated. On the contrary, the young monkeys felt more stress in this together housing situation than the aged, and they showed more behaviors to reconcile with her aged partner. The data clearly showed that the higher tension the young felt affected their immunological function.

The aged cynomolgus monkeys in the Tsukuba Primate Center (TPC) are very important and highly refined resource for the scientific study of aging. They are expected to be investigated from various aspects of science. This study wasconducted in collaboration with Dr. Cho, Dr. Terao (TPC), Ms. Tokairin (HOXAN), and Dr. Noguchi (Tsukuba University).

Page-25 Body temperature in infant cynomolgus monkeys

Takahiro Ono

Body temperature is one of the important factors for health management of infant monkeys. We surveyed the time when infant cynomolgus monkeys become to maintain their

body temperature by themselves. The results obtained are shown in Fig. 1. The body temperature of the neonates of 0-day-old and 1-day-old fell most, however that of the 7-day-old infants fell a little and recovered after 120 min.

Table 1 shows the body temperature immediately after maternal separation. Significant decrease of the body temperature with time was seen in the infants under 5-day-old.

Page-26 Report on a symposium

This May, Dr. Tadashi Sankai participated a symposium on IVF and embryo implantation in nonhuman primates held at Tigard, Oregon, U.S.A. He presented "Ovarian Superstimulation and In Vitro Fertilization in the African Green Monkey" in the poster session (Photo). The symposium was very fruitful and stimulative for him, he reports.

Page-27 Q and A

We have received questions about the characteristic of nonhuman primates from many readers of TPC NEWS. Now, we open the corner of Questions and Answers to reply to those questions.

(Q) Would you tell me the reference value of hematology and serum biochemistry in the cynomolgus monkey?

(A) It is rather difficult to answer this question, because those values are affected by physiological conditions of monkeys such as the origin of animals; wild-originated(2) or laboratory-bred, caging conditions (3), feeding conditions (4), age of animals (5), pregnancy (6) and so on (7). And furthermore, some species such as the squirrel monkey shows annual changes in hematological and serum biochemical values. Please refer the following reports.

References

1) Yoshida et al., (1983), J. Growth 27: 166-169.

2) Yoshida et al., (1989), Exp. Animal 38: 259-262.

3) Yoshida et al., (1990), Exp. Animal 39: 21-26.

4) Yoshida et al., (1988), Exp. Animal 37: 39-44.

5) Yoshida et al., (1986), Exp. Animal 35: 329-338.

6) Yoshida et al., (1988), Exp. Animal 37: 257-262.

7) Yoshida et al., (19869, Exp. Animal 35: 455-461.

(Q) What kind of commercially supplied human hormone kits is available for measurement of cynomolgus monkey serum hormones particularly protein hormones?

(A) We applied several human kits to measure cynomolgus serum hormones. Some of them were available, and the results were tabulated. It is necessary to confirm the availability of each human kit when we apply it for measurement of nonhuman primate hormone. (Takashi Yoshida)