TPC NEWS Vol.4, No.2, Fall 1985,
(Whole Number 8)
(
English Summary )
Page-3
Essay: Coexistence with aged monkeys
As of June of this year, the oldest cynomolgus monkeys, who are being
kept at TPC and whose exact birth dates are known, are 22 years and four months
old with male, 20 years and six months with female.
Regarding wild-originated breeders, the oldest female and male are
estimated to be 22 to 25 years of age. It
is generally accepted that the life span of the macaque would be 25 to 30 years. Thus our old monkeys may be worthy of being celebrated for
their long lives.
At TPC, we intend not only to hold a very large number of young monkeys
but also to keep as many 'aged monkeys as possible, because we think that old
monkeys are able to b" a suitable animal model for studies aging and
senility in man.
In general, the orthodox method of animal experiment in studies of aging
and senility are to observe and measure natural changes with increasing ages in
morphology, functions, behaviors and some reactions to a certain treatment. To
adopt this method of study is rather easy, when we deal with laboratory animals
of comparatively short life span, such as mice. Usually, however, we can not
apply this method to animals of long life like primates. It is almost impossible
to perform follow-up studies on such animals throughout their lives, in other
words, to adopt a longitudinal method of study, judging from ordinary duration
of research activities of a scientist. So it is impossible for us not to take a
transverse way of study in which we employ animals of different ages at a
certain moment.
Naturally, this method of study would require maintaining and
conditioning many monkeys of different age classes. To satisfy this prerequisite
is rather difficult for ordinary laboratories or facilities of experimental
animals in universities and research institutes.
I think, fortunately, TPC has this prerequisite at the present time.
But to keep this condition from now on is not easy because it needs
special care, area, budget and patience.
By the way, I, being in..1%1 late. fifties, have begun to feel my own
"age". Although I keenly
feel that more much time is necessary for me as a scientist to develop my work,
'I will have to retire from TPC within five years.
Therefore, I wish that TPC could keep those aged monkeys safely as long
as possible and I make their biological characteristics as clear as possible.
These works will remain to my successors.
If the young staffs of this center who are and will be working with aged
monkeys would have thought about their own way of life through cares or works on
aged monkeys, in addition to satisfying their will of scientific research, then
it would be my great pleasure.
Page-4
Breeding Topics: The third primate species kept at TPC---Common squirrel monkey
The common squirrel monkey is a species of the New World monkey whereas
both the cynomolgus and the green monkeys are 01d World monkeys. The latter two
species live on the ground but the squirrel monkey lives usually in trees. Adult
female squirrel monkeys weigh 600-800g and males about 1kg.
Birth weight is around 100g. They are usually have one baby at a time.
The nursing behavior of
this species is unique. Mother monkeys carry their babies on the back.
When they suckle they draw their babies to their breasts.
They scarcely hold babies in their arms even when they give milk.
Unlike the cynomolgus and green monkeys , the squirrel monkey has
seasonality of breeding. They mate
from late fall to winter it the northern hemisphere and have babies from spring
to early summer. Many studies have
been done on the breeding seasonality by using squirrel monkeys.
But the exact mechanism to provoke this seasonality is still unknown .
At present, the squirrel monkeys kept at TPC are 9 adult males and 39
females. They were imported during
from Feb. '80 to Nov. ' 82. Until
today 31 male and 16 female offsprings were born in this center.
Since we introduced squirrel monkeys to our colony, we have maintained
the species on the basis of the breeding systems established for the cynomolgus
monkey. The breeding performance are shown in the table below. The items given are, from the top column to the bottom, (1)
the period during which we found the pregnancy, (2) the period of delivery, (3)
the number of delivery to the number of female breeders. The number of delivery has surely increased.
However, further investigations are needed to determine whether or not
the seasonality has become less marked for these five years.
Colony bred squirrel monkeys born in 1981 has been fertile. We
have already gotten 27 infants up to August 7 of this year.
Page-5
A Survey on the Incidence of Antibody to Simian T-Cell Leukemia Virus in
Cynomolgus and Green Monkeys
Retrovirus having close antigenic similarity to Adult-T-Cell Leukemia
Virus (ATLV or HTLV-Type 1) has been found in various 01d World monkey species .
It has been proposed to call the virus Simian T-Cell Leukemia Virus (STLV)
.
Surveys on the incidence of an antibody to STLV by the indirect immuno-fluorescence
method were conducted with wild originated monkeys.
[ Materials and methods ]
Sera used were collected from 651 cynomolgus monkeys of wild origin which
were imported from South-east Asia in 1968 to 1982 and thereafter kept in our
center, 150 newly imported cynomolgus monkeys from the Philippines, 45 African
green monkeys of feral origin imported in 1979 to 1981 and one to four years old
69 offsprings born from these imported wild green monkeys .
The antigen used was MT-1 cell established by Miyoshi et, al.
MT-1 cells spread on slide glasses were dried and treated with acetone
for 10 mmutes at room temperature .
FITC labeled anti-monkey IgG goat serum diluted 170 times was used as the
second serum.
[ Result ]
Wild Originated
Cynomolgus Monkeys: Of 651 animals
maintained for a long period, 76(11.7%) were positive.
According to their countries of origin, 52(23.9%) of 218 Indonesian
monkeys, 22(9.4%) of 233 Malaysian monkeys and 1(0.5%) of 198 Philippine monkeys
were positive. A Cambodian monkey, though there was only one in our colony, was
positive . But, one animal from Thailand was negative .
Newly Imported Cynomolgus
Monkeys : Thirteen (8.7%) of 150
animals were positive.
African Green Monkeys of
Wild Origin: Thirty-two(70%) of 46 animals were positive.
They had already been positive at the time of arrival at TPC.
Colony-bred African Green
Monkeys: All 69 animals were negative. .
[Conclusion]
As for the wild originated cynomolgus monkeys kept for a long time, the
positive rate differed with the country of origin, But further studies are
needed to determine whether or not these differences show the real state of STLV-contamination
in those countries. Definite reasons for the large difference in the antibody
incidence between newly imported Philippine monkeys and long-maintained
Philippine monkeys is unknown at the present moment.
High positive rate of the wild originated African green monkeys indicates
that when we handle African green monkeys we should be more careful from the
standpoint of biohazard control, It is still unclear why all the colony-bred and
-reared green monkeys were negative, It may be considered that these monkeys
were still too young or there is no virus transmission from mother monkeys.
Periodical examinations are needed to clear these problems.
Page-6
Introduction of Facilities - Facility for incineration
At TPC sewage water from
animal rooms amounts to 2000 mg a day, and drainage from research laboratories
amounts to 20 m a day. We have a sewage treatment facility (See, TPC NEWS Vol.,
1 No. 1 ) and a facility for incineration system to treat the leftovers and
excrement separated from the sewage water by automatic scriveners.
In the incineration building, there are a main incinerator and a
sub-incinerator. The main incinerator has two furnaces. One of the furnaces is
for combustion and the other for re-combustion. The sub-incinerator is used to
dispose of ordinary rubbish. The combustion furnace of the main incinerator is
1.9m wide, 2.9m deep and 1.9 high. The
chamber of this furnace is equipped with four jet burners to get the best
combustion efficiency. The inner
wall of the furnace on which temperature comes to 700
is made of firebrick and the outer side is covered with heat-proof bricks.
On the ceiling, a way-in is fixed with a dumper. The re-combustion
furnace having two jet burners is for burning up odors and gasses resulting from
imperfect combustion in the furnace I mentioned above.
Solid filth is carried by a skip conveyor to the way-in on the upper
surface of the incinerator and falls into the furnace.
Carcasses of autopsied animals are also incinerated in this furnace.
They are thrown into the furnace through the other door fixed on the side
wall. The sub-incinerator has no burner, however, once the rubbish is kindled it
is completely burned up owing to a
chimney eleven meters high.
These incinerators have worked well without any trouble and accident
since they were installed seven years ago.
This is due to earnest efforts of maintenance,
Moreover, we have adopted a room of 28 m3 to keep solid waste
or carcasses of animals at 5
for the occasion sit which the incinerator does not work.
Page-7
Homeland of the Cynomolgus Monkey - My field study of the cynomolgus monkey in
Indonesia
The time when I began to deal with cynomolgus monkeys in my research work
was coincident with the time when TPC was established, through the process of
studies on phylogeny of the Japanese monkey by the method of population
genetics. I became aware of the
usefulness of cynomolgus monkeys, especially the ones living in Indonesia as
important research materials.
For these two decades, knowledge concerning genetic variation of natural
population has been rapidly accumulated owing to the advanced technique of
electrophoresis. Many series of studies are being carried out with various
animal species in order to elucidate a number of problems such as maintenance
mechanism of intra-species variation, population structure, specific divergence
and phylogenetic relations.
The results obtained from the studies using Japanese monkeys have
revealed that (1) a troop as a social unit of the Japanese macaque is open to
other troops in respect of breeding, (2) the genetic variability within a troop
is low and (3)the genetic differentiation between troops is limited.
Comparative studies using other primate species that are close relatives
of the Japanese macaque and living in boundary islands in the distribution area
of macaques were needed to determine whether or not those findings with the
Japanese monkey were recognized also in other primate species.
That is the very reason why I chose the cynomolgus monkey in Indonesia as
my research material.
My field work needed capturing monkeys so that I could collect blood
samples from troops of wild populations. I
began my research plan in seeking cynomolgus monkeys which were habituated to
humans in Sumatra, Java and Bali Island. Then
I found that these three islands had their own characteristics in the
relationship between monkeys and men.
For example, in Sumatra Island, even though vast tropical forest is still
existing, cynomolgus monkeys are now exposed to serious environmental conditions
such as destruction of the forest by road constructions and capture for
exportation. The living condition in this island is so severe that people seemed
not to have any surplus to feed monkeys. Therefore,
it was so difficult to find cynomolgus troops composed with habituated monkeys.
However, harvesting bananas by using trained pig-tail monkeys was a
memorable custom in Minancabau district in the state of West Sumatra. I asked
people whether cynos were able to be trained for such a custom.
They replied that pig-tails were wiser than cynos, This reply hurt my
feeling a little because I had been attached to cynos.
Java Island is one of the most overpopulated zones in the world.
Differing from the sight of Sumatra, I could find inhabited localities in any
mountainous place of Java far from the highway.
In Sunda Islands, east of Sunda Strait, the cynomolgus monkey is only one
species of the genus Macaca. Although
Java is an overpopulated area, I had many chance to meet cynos there.
Even in Jakarta, the capital of six million population, I saw cynomolgus
monkeys living vigorously in the mangrove forest. The cynos which live under
symbiotic conditions with man reminded me of a scientist's comment that the
environmental adaptability of the genus Macaca can be expressed by the
words, "weed-like nature'.
On the other hand, Bali is an island of Hindus and rice fields.
Temples called Pula are in villages of Bali.
In the woods surrounding those temples I often saw cynomolgus monkeys.
Villagers' feelings seemed not to be hostile to monkeys in spite of
damages caused by monkeys in rice fields. It
may be because that people have respect for Hanuman, a monkey god.
There even are some Hindu temples that are famous for monkeys. The situation in Bali which monkeys and men live in peace
with religious background was utterly different from that in Sumatra and Java
Island.
Then I visited Lombok and Sumbawa islands, but I could not have any
chance to see "habituated" monkeys.
So I decided to carefully observe feral monkeys and to capture them,
Although both Lombok and Sumbawa islands are dry districts, monkeys have adapted
themselves to such bad natural environment.
As a result of surveys in these five islands, I could collect blood
samples from 456 animals of 29 troops from 10 habitats.
Electrophoretic analyses of 29 kinds of proteins which were considered to
be controlled by 33 gene-loci demonstrated the presence of polymorphism with
regard to 19 gene-loci. Frequency
distribution of certain genetic markers in several population categories showed
that the troops of the cynomolgus monkey in Indonesia were open units in respect
to breeding like the troops of the Japanese monkey.
Genetic exchange due to traveling of adult male monkeys among troops
could be considered. This
supposition was also supported by the field observation in Sumatra and Borneo.
On the other hand, quantitative analyses of genetic variability in the
troops revealed their genetic similarity and dissimilarity to the Japanese
monkey. As shown in Table 1, the
genetic differentiation of the troops of cynomolgus monkeys was three times
higher than that of Japanese monkeyfs. These
results mean that the genetic structure of members in a cynomolgus troop is not
uniform. Furthermore, the definitive point in differentiating them from the
Japanese monkey is that a remarkable difference in genetic structure was
observed among troops in different islands.
Table II shows the structure of genetic divergence among the cynomolgus
monkey populations. Here, I supposed such a hierarchial population structure that
the whole population is just a mass of insular populations and an insular
population is just as a mass of troops. The
relative genetic divergence among insular populations was calculated based on
the estimated genetic frequency of troops. These results showed that the relative divergence of the
cynomolgus monkey population was 41.3%, whereas that of the Japanese monkey
population in Honshu, Shikoku and Kyushu was much lower, that is only 2.7%.
In short, my field studies in Indonesia have revealed that the cynomolgus
monkey has genetic characteristics, that is the difference in genetic structure
is large among different local populations in different islands.
When we establish nonhuman primates as laboratory animals, the genetic
differentiation of great magnitude is a very useful factor for using in various
experiments. Moreover, many genetic markers kept in nonhuman primates are
expected to be a strong weapon for genetic analyses.
On the other hand, when we notice the large genetic differentiation among
local populations, breeding nonhuman primates with each group divided by their
country of origin is of great significance in maintaining genetic variabilities
and in doing phylogenetic studies. Now,
I am very interested in how "weed-like nature' of the cynomolgus monkey,
with which I was strongly impressed in my field work, will be developed in the
process of laboratory conditioning.
Page-9
A Comment on My Research - Experiences of biochemical examinations on the blood
of cynomolgus monkeys
Foreword:
In our breeding and rearing facilities, biochemical blood-examinations
are carried out to grasp general health conditions of animals.
Now I am in charge biochemical serum examinations using an auto-analyzer.
As everybody knows, an auto-biochemical-analyzer is useful to obtain
simultaneously and speedily many data, of many items using a minute quantity of
sample. But an auto-analyzer is
only machine which calculates the data resulting from the reaction of reagents
to test-materials. Therefore, when
we judge the health conditions of animals from the data, we have to know
beforehand the normal changes with increasing age, differences between males and
females, and so on. In this paper,
I will describe my experiences associated with blood-examinations of cynomolgus
monkeys using an auto-analyzer,
1. The influence of
freezing and thawing.
At TPC, periodical health checkups are carried out on every Thursday
morning. The blood taken is kept all night at 4.Sera
are separated the next morning and are analyzed in the afternoon of the same
day. Routine analysis using an auto analyzer is performed once a week.
As for the animals suspected to be suffering from some diseases, their
sera are examined also by some method other than the auto-analyzer. When we can
not immediately examine the sera they are frozen and preserved until the next
routine analysis. Moreover,
re-examination of preserved 't sera is sometimes needed.
So I tried to examine the influences of freezing and thawing and of the
preservation period.
Sera from several male cynomolgus monkeys were mixed and then divided
into 1 m1 aliquot, The items and the unit of measurement are shown in Table 1.
The results about GPT are given in Fig. 1.
Symbol o (solid line) shows the data taken after freeze-preservation at
-804: and symbol + (interrupted line) at -20.
A gradual decrease in GPT activity was observed during one-year
freeze-preservation at -80:
and a very rapid decrease was observed at -20.
GOT had little change at -80:
while it decreased during the long preservation .period at -20
ALP decreased gradua;1y after eight months regardless of the preservation
temperature. TP, ALB, BUN, GLU and T-CHO showed no remarkable change throughout
the preservation period of one year. The
values of F-CHO and TG tended to rise with the increase of the preservation
period. When we analyze
frozen-preserved sera we have to be careful in the judgment of the data obtained
with regard to some items.
2. The influence of
concentration before measurement.
When I was inexperienced in operating the auto-analyzer I often could not
finish analyzing materials within a day after I got the materials.
Under such circumstances, I had to measure them again the next day.
And I found that the data obtained on the next day seemed to be a little
higher than those obtained on the day before.
I thought that the cause to increase the value would be the concentration
of the materials during the time before measurement.
I examined the influence of the concentration on the values when
materials were left for a long time at room temperature.
Sera were taken from ten animals. Three
aliquots of 300, alwere prepared with each serum. One of them was analyzed on the day the blood was taken.
The rest aliquot samples were left for six hours at room temperature, and
then kept at 4.
On the next day, one of the rest aliquots was measured. Another one was again left at room temperature and kept
overnight at 4:
and then analyzed. The results are
given in Table 2.
Of course, the concentration of test-materials can be influenced by the
temperature and humidity of a room where samples are left.
Therefore, the data may be affected by the difference in type of the
analyzer used as well as by season. Now,
that I have become accustomed to the operation of auto-analyzer, I make it a
point to set a half or one-third of all of the materials in the tray and not to
place them at a time when I measure a lot of samples.
3. The physiological
adjustment of the wild originated animal to the artificial environment.
One of the problems in wild originated animals is the physiological
change resulting from their transference from a natural environment to an
artificial one. At TPC, the
quarantine period of at least three months is set for them.
So I examined the changes of various physiological parameters in
newly-imported cynomolgus monkeys during the time of arrival at TPC to the 3rd
and 6th month after arrival. Two
typical changes are given in Figs. 2 (BUN) and 3 (ALB) .
Generally, both male and female BUN were low on arrival, In some
exceptional cases they-were high. After
three months, the animals showed neither an extremely high level nor an
extremely low level Six months later the values rose slightly as a whole.
These changes suggest that the animals generally be-came stable in their
physiologic state. As for
ALB, the changes of the values showed the same pattern as those of BUM. It can be said that the newly imported monkeys including some
with ill health conditions recovered three months later and adjusted themselves
to the artificial environment after six months.
As for serum Ca, I had an interesting experience related to its
concentration. Fig.3 shows the
frequency distributions of serum Ca concentrations on arrival in four different
groups of newly imported cynomolgus monkeys. These four groups were imported
almost at the same time. Lot 10-3 differs from others in regard to the country
of origin and shows lower values.
The average estimated age of animals in Lot 10-3, judging from dentition,
was younger than that in other lots and Lot 10-3 was lower in weight, too.
Therefore I examined the relations between serum Ca concentration and age
and/or weight of animals, but I could not find any significant relation.
At the end of the quarantine period, however as I presented in Fig. 5,
all animals including those of Lot 10-3 showed the values around 9.8 mg/d1. Any
way, it is highly probable that the serum Ca level of imported wild monkeys can
be improved by the feeding conditions of TPC during the quarantine period.
4. The relation between
age and determined values in colony bred monkeys.
It is important to know the relation between age and determined values.
I made transverse studies on the relation using 555 female and 531 male
cynomolgus monkeys bred-and-reared in our colonies.
The item that exhibited the most remarkable change was ALP(Fig. 6).
ALP of infant and juvenile monkeys showed both high activities and wide
individual variations. The
activities, however, markedly decreased after the age of 4 to 5 years. At the age of 6, the activity dropped to one- sixth of the
activity at the age of one or two. The
activity declined a little earlier in females than in males.
As Figs. 6 and 7 show, the time when ALP became stable at low value and
the time when the weight increase reached the plateau are almost coincident with
each other. These results suggest
that the cynomolgus monkey is fully matured by the age of six.
By the way, it has been revealed by the examination of sex-steroid
hormonesf level in blood that the sexual maturation of the cynomolgus monkeys
is attained at the age of about 4. Also
in this respect, females mature earlier than males, and the time of maturation
corresponds with the time of rapid decrease of ALP.
Afterword:
The knowledge I described above resulted from the examinations performed
with cynomolgus monkeys. At TPC,
African green monkeys and squirrel monkeys are kept besides cynomolgus monkeys.
These two additional species are now small in number, but we will be able
to carry out the same examinations using them in a few years.
I have performed several basic examinations to obtain reliable data by
which we can grasp health conditions of animals.
From now on I constantly have to make every effort to re-examine the
conditions for measurement as well as examination items themselves.
Page-13
A Special Article - Studies on basement membranes and laminin components -
Usefulness of the nonhuman primate.
During the past decade the study of the chemistry and biology of basement
membranes has been influenced by the discovery of cell attachment factors such
as laminin, which is the surface component of the basement membrane.
The isolation and purification of the intact laminin from normal tissue
has been the most difficult task and key step to investigate the function of
laminin. I was one of those who had
trouble isolating laminin from normal tissues. Fortunately,
I developed a system to isolate intact laminin from human placenta for the first
time. But 1 have not been
successful in isolating laminin from other tissues yet.
From the experiences gained from human placenta, we have expanded our
research into several other animals. We
have compared the nature of laminin from cow, rat, and mouse placentas.
These are similar to each other, but are distinctively different from the
laminin isolated from tumors of the same species.
We would like to expand our research into an animal model system which we
can apply to human diseases. The
best possible model for this is a monkey. Preliminary
data indicated that monkeys placental membranes and their laminin content are
very close to that of the human.
If we can use a monkey system to develop the experimental design, we can
gain knowledge about the human system which we can not obtain from other
animals.
I have been looking for such an opportunity for quite some time.
Then, I realized that my close friend, and high school classmate, Dr.
Fumiaki Cho, has been working in Tsukuba Primate Center, a new modern facility,
where a large number of cynomolgus monkeys have been bred successfully.
Fortunately enough one of their research projects involved C-sections of
term pregnancy. When I went to
Japan in 1984 to visit several universities to give seminars, I also visited
Tsukuba Primate Center and asked if I could get permission to obtain fresh
monkey placentas and process them on site.
Not only was my request granted smoothly, but.
I also got warmhearted cooperation from Director Dr. Honjo and several of
his Sr. staff members. As a result,
I have obtained the necessary number of monkey placentas from which I could
isolate laminin.
This time I was asked by TPC NEWS editorial committee to write a general
description of basement membrane and its component laminin, including my own
area of research.
The basement membrane is a extracellular matrix which is a necessary
component of functional tissues. These
cells, namely endothelial cells and epithelial cells, must attach to the
basement membrane, enabling the basement membrane to work as a selective barrier
between inside of the membrane and the outside.
Blood vessels, for example, are nothing but a basement membrane structure
which eliminate waste materials from tissues.
The same blood then
brings in necessary nutrients, including oxygen. Several diseases, including diabetes mellitus, cause changes
in the basement membrane. These
abnormal basement membranes are thick(3-5 times of normal) and leaky to the
extent that there is less barrier between the inside of the blood vessels and
the outside, Large molecular weight proteins can freely leak out in such a
terminal situation. However, at
this time we don't know how these changes to the membrane and cells happened.
In many tissues, including eyes, brain, kidneys, nerves, and skin,
basement membranes play key roles in a variety of disease conditions, This is a
reason that scientists working on basement membranes come from a variety of
backgrounds, The research itself has expanded explosively in the last ten years.
We held the first international conference on basement membranes in Japan
in the summer of 1985.
The center of the basement membrane (lamina densa) contains collagen Type
IV, while the outer layer (lamina rarae) is covered by laminin, proteoglycan and
others. These surface components, such as laminin and proteoglycan,
also work as cell binders or as biological glue.
Many diseases such as nephritis, are actually basement membrane diseases.
One of the recent developments of basement membrane research is cancer research.
In the case of metastasis, the tumor cell must attach and break through
the basement membrane to get into blood vessels or lymphatic channels.
There, in order to survive, the cancer cell must again attach to the
basement membrane to get out of the hostile blood stream.
The key step in metastasis is the tumor cell attachment of the basement
membrane, If this mechanism were known we could control the spreading of tumor
cells in our body. Collagenase
production by tumor cells, laminin receptors on the tumor cell surface have been
investigated extensively. The
investigation of the tumor cell surface, and oncogene, are important but studies
of basement membranes are equally important. Basement membranes are directly involved in development and
differentiation of the tissues. However,
detailed structure and function of basement membranes are not 'yet known. The
majority of investigators who are working on laminin are using tumor systems,
because these tumors produce abnormally large amounts of laminin, which may be
defective. These tumor laminins are
soluble and easily purified. On the other hand, normal tissues contain only
small amounts of laminin and this laminin is not easily soluble. It is difficult to isolate the intact molecule from normal
tissue. Tumor laminin consists of
two subunits A (400,000 MW) and B ( 200,000 MW).
Laminin isolated from normal placenta has three subunits A, B, and M (
300,000 MW). The M is taken from the first letter of my daughter's name, Mika,
who named this subunit,
If the absence of the M subunit in tumor laminin is not due to tissue
specificity, but only due to neoplastic transformation, the subunit M is a
marker protein, which many scientists have been looking for.
However, subunit M has only been detected from placentas (human, cow,
rat, mouse and monkey) and because other tissues are difficult to extract, the
presence of laminin M has not been proven yet.
On the other hand, we have examined only five tumors (human, rat and
mouse). Therefore, we cannot
definitively conclude this difference is due only to tumor transformation.
We have just started a tumor project to elucidate or confirm our initial
findings. Monkeys will be useful in
this project because tumors can now be induced in healthy animals.
Another interesting project is to confirm one of the hypothesis that
eclampsia, sudden contraction of the uterus which leads to the death of the
fetus, is due to the mother's antilaminin antibody rejecting the placenta.
The monkey is the perfect animal model. Other animals are less desirable
because of differences in gestation period, placental structure and function.
As a conclusion, I have described the importance of basement membranes
and the area of my own research. I
have also mentioned how monkeys can be useful as an experimental model for us.
Even though I have never approached monkeys before, I came to the Tsukuba
Primate Center. Now, I am kind of
familiar with those monkeys and monkey tissues. This familiarity is largely due
to the warm cooperation given to me from the efficient professionals who are
operating Tsukuba Primate Center.
I hope that the usefulness of monkeys as a medical research model is more
widely recognized among basic medical scientists. I would like to extend my
appreciation to several key staff members who have been patient with me and
guided me in accomplishing my initial purpose at the Tsukuba Primate Center.
Thank-you again.
Page
15 Overseas Topics - A side of the animal protection movements in the U.S.A.
A short paper titled "How Radical Animal Activists Try to Mislead
Humane People" has been presented in Laboratory Primate Newsletter,
23(3) '84.
The authors, D. Caroline Coil & Neal E. Miller, have reported the
result of an survey, which had been conducted to determine how true and typical
the accusations being stated in a publication of the animal activists group
were:
The survey covered every article (a total of 608) appearing for the last
five years in the Journals published by the American Psychological Association.
The accusations and the percentage occurrences of articles in which such
accused treatments and/or facts were reported were:
(1) "Animals are
given intense, repeated electric shocks which they can not escape, until they
lose the ability to even scream in pain any longer"- 0.0%.
(2) "They are
deprived of food and water to suffer and die slowly from hunger and
thirst"- 0.0%.
(3) "They are put in
total isolation chambers until they are driven insane or even die, from despair
and terror"- 0.0%.
(4) "They are
subjected to crushing forces which smash their bones, and rupture their internal
organs"- 0.0% (5) "Their limbs are mutilated or amputated to produce
behavioral changes"- 0.0%.
(6) "They
are the victims of extreme pain and stress, inflicted upon them out of idle
curiosity, in night marish experiments designed to make healthy animals
psychotic"- 0.0%
The authors have told that none of the
allegations 'were found be true in any of the 608 articles. They also have
demonstrated the contributions and needs of the animal experiments to the
progress of science and medicine, introducing various facts and data.
Then they have concluded as follows: Nobody wants to see
animals suffer needlessly nor do they want progress toward the elimination of
suffering in human to be halted. Therefore, it is essential to be totally honest
in the representation of facts concerning animal welfare in research...... By suggesting the false and by suppressing the true, radical
animal activists are diverting the energy and funds of humane groups away from
areas where animal abuse is common (such as the abandonment of 10 million pet
dogs and cats each year to die of starvation, disease, and road accidents) in
order to focus upon an area in which it is rare.
We can see a side of the relationship between animal protection movements
and behaviorological studies using laboratory animals in the
Page-16
Case Report - Lung mite infection
Recently, as far as our own data are concerned, the incidence of lung
mite infection in imported wild cynomolgus monkeys has strikingly decreased.
From 1982 through 1984 no case of this infection has been found at the
autopsies of 150 dead wild-originated monkeys, whereas the positive rate in the
survey carried out in 1963 by Honjo et al, was about 22%. The causative mite, Pneumonyssus
simicola belongs to the Mesostigmata.
It usually parasitizes in lungs, whereas ordinary mites parasitize
in skin and hair. The lesion in the lung is pale yellow in color with a slight
gloss and slightly upheaval, showing clear demarcation, The size of the lesion
ranges from0.3 to 1.1cm with the mode of 0.3 cm(Fig. 1).
The mites are found in the yellowish pus on the cut surface of lesions.
The pathological findings of the lesion are as follows: the round cells
crowd around the mite, making circular layers.
A lot of brown pigment is observed.
Smooth muscular tissues are often recognized in the lesion (Fig. 2).
Since male and female adult mites as well as larvae are found in the
lesions, this species of mite appear to live their whole life in the lung. The morphological characteristics for the classification of
this mite are the presence of the stigma with short peritrema and of the dorsal
plate of a shape of shield on their back (Fig. 3). It is thought that the lesion resulted from the movement of
mites in lungs (Fig. 4), and the route of infection in monkeys might be nasal or
oral. After the infection, the
mites appear to cause lesions in peripheral bronchi.
As yet there has been no reported case of human infection by the mite
species. Judging from the infection
cycle, I think, this lung mite is not so important for man from the view point
of zoonosis. As one of the reasons
relating to the decrease in the incidence of lung mite infection in imported
wild cynomolgus monkeys, it can be thought that Cambodian monkeys which showed
high positive rate have been unable to be imported.
However, there may be some other socio-biological reasons for the
decrease.
Page
17 A Clinical Commentary by a Veterinarian - Wounds found in a Mischievous
monkey
One morning, when I entered room no.5. I
smelled a strong odor of blood. I
thought that there might be a monkey who had wounded finger or some other body
part. I searched for the monkey.
In a group feeding cage, I found a male cynomolgus monkey aged 4
and half, whose leg was covered with semicoagulated blood.
Immediately I and two animal technicians moved the monkey into another
cage and anesthetized him. Then I carried the monkey to the treatment room and
examined his wound, A horizontal slash of 5cm width and 2cm depth, as if it was
cut with a sharp knife, was found at the left calf of the monkey.
Bleeding from the end of a vein was still going on.
I first fixed forceps at the broken ends of the vein. The tips of the
forceps had been covered with vinyl tubes lest they should break the blood
vessels. Then I sutured the deep part of the broken muscle to draw up
both ends of the blood vessels. Suturing
small blood vessels of 1-2mm diameter without any special surgical instrument
required very difficult techniques. After
suturing I took off the forceps at the cut end of the distal side then at the
end of the proximal side. Bleeding
was not seen any more. However, I
had no confidence in completely maintaining the tubular structure of blood
vessel. The only thing I could do was to wish that the formation of thrombus
would not happen. As I was suturing, I thought that if' the vessel was
obstructed, a bypassimt1g vessel would compensate for it.
I finished suturing the
muscle, the fascia and finally the skin by button suture, thus I accomplished
everything related to the treatment. Then, the monkey was kept in an individual cage.
He recovered from the wound after a week.
About one month later, the monkey was again carried into the
treatment room, because he had a 5 cm long cut on his 1eft calf again.
What was the cause of these wounds?
Several days passed since he had recovered from the second injury.
While I was observing his behavior, his leg appeared suddenly from a hole
of his food box. Food boxes used in this center were fixed on the front surface
of cage. The monkey put his leg through the hole to take food probably to kill
time in his boring schedule.
Wounds caused by monkey's own mischievous behavior sometimes happen, A
fracture case I reported in TPC NEWS Vol.3, No.3 is an example of them.
Generally, monkeys fumble with their cages' doors, partition boards,
water nozzles, keys and other things as their playthings.
They are geniuses in playing.
By the way, the food box of the wounded monkey was taken off and his food
was put directly on the cage floor. I've
never seen him in the treatment room since that time,
Page-18
"The Bullied" in the Monkey Colony at TPC
Today, "bullying"
is a serious problem in human society. It
is seen in the monkey society, too.
"The bullied monkeys" in our colony are mainly one to three
years old animals kept in group-feeding cages.
They correspond to from primary school pupils to senior high school
students in human society. The
bullying monkeys are, of course, the far bigger ones in the cages.
"Bullying" is done in crafty ways.
It happens, for example, when no animal technician stays in the animal
room or at the time just after the lights are turned off.
The bullied can not easily take food.
One Sunday morning in May this year, an animal technician found a dying
monkey. All of his hair had be6h fallen out: and his body was already cold. He
died soon in spite of our tender care. He
was two years and two months old .
Another case was found in June. The
bullied monkey, one year and eight months old, was the smallest in his group
cage. Fortunately, he escaped death by appropriate treatments, I
think that we urgently need to take adequate countermeasures so that no more
bullying occurs.