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National Institutes of Health(U.S.). Division of R.

Report of program activities : National Institutes of Health. Division of Research Services (Volume 1978) online

. (page 13 of 15)
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that concentration. As PPD concentrations increased, the reaction

intensity plateaued near 2 mg per milliliter and increased very little

with concentrations up to 6.5 mg per milliliter, never reaching the (

intensity of FSMT. Both positive or suspect reactions to MT were elicited

up to three weeks before those to PPD.

The results of lymphocyte transformation testing have not been completely
analyzed. However, preliminary information indicates that the tuberculin
testing interferes with lymphocyte stimulation. Whether this is dose
related is uncertain. It will be studied further.

The findings to date indicate the erythrocyte sedimentation rate increases
in all reactors, up to 22 mm per hour in one case. Other clinical
pathologic parameters are being studied.

Significance : The study will permit evaluation of the most effective
product for detection of tuberculosis in naturally exposed nonhuman
primates.



>



V,



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
HEALTH, EDUCATION, AND. WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
NTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RS 00015-03 VR



PERIOD COVERED

October 1, 1977 to September 30, 1978



TITLE OF PROJECT (80 characters or less)

Defining the Nude Mouse Model



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER



PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI :
OTHER:



R.A

C.T

J.R

A.M

C.K

H.J

P.

R.



Whitney,
Hansen

Ganaway

Allen

Hsu

Alter
Holland
Purcell



Jr.



Chief VRB DRS

Geneticist VRB DRS

Veterinary Microbiologist VRB DRS

Chief, CPS VRB DRS

Ft. Detrick, Maryland FCRC

Blood Bank CC

Blood Bank CC

LID NIAID



COOPERATING UNITS (if any) „,..,.,,

Laboratory of Infectious Diseases, NIAID

Blood Bank, Clinical Center „ , . TT „ ,.. ,, , =

Dept. Laboratory Animal Medicine, Johns Hopkins U., Baltimore, Maryland

Frederick Cancer Research Center, Ft, Detrick, Maryland

lab/branch

Veterinary Resources Branch _

SECTION

N/A



INSTITUTE AND LOCATION



DRS, NIH, Bethesda, Maryland 20014



TOTAL MANYEARS:





PROFESSIONAL:




OTHER:



CHECK APPROPRIATE BOX(ES)
Q («) HUMAN SUBJECTS

□ (al) MINORS - □ (a2) INTERVIEWS



□ (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

A congenic strain of mouse crossed with CBA inbred will be used to again attempt
to identify an animal model for human hepatitis A and B . This congenic strain
CBA/nude will lack the thymus and T system of the nude and also lack some
elements of the B immune system inherent in the CBA mouse.

Project has been suspended while awaiting production of congenic CBA/nude mouse.



135



PHS-6040

__



PROJECT NUMBER [Do NOT use this space)



>,..... L/L.r«rtiMtMl Or
HEALTH, EDUCATION, AND WELFARE
PIJPI.IC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER

ZOl RS 00016-02VR



PERIOD COVERED

October 1, 1977 to September 30, 1978



TITLE OF PROJECT (80 characters or less)

Characterisation of a New Viral Disease of Rabbits



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT

PI : J. D. Small Animal Disease Investigator SAS VRB DRS

OTHER: R. A. Squire Johns Hopkins University

L. Aurelian Virologist Johns Hopkins University

J. D. Strandberg Pathologist Johns Hopkins 'jferiversity



COOPERATING UNITS (if any)

Johns Hopkins University School of Medicine, Baltimore, MD



LAB/BRANCH

Veterinary Resources Branch



SECTION

Small Animal Section



NSTITUTE AND LOCATION

DRS, NIH, Bethesda, MD 200H



TOTAL MANYEARSs

1.0



PROFESSIONAL:

1.0



OTHER!



0.0



CHECK APPROPRIATE BOX(ES)
□ (a) HUMAN SUBJECTS

O (al) MINORS □ (a2) INTERVIEWS



□ (b) HUMAN TISSUES



[3(c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

The goal of this project is to isolate and characterize the agent responsible
for a disease recently detected in rabbits , describe the clinical course,
define the lesions, study the mode of transmission, and define the host range.
Work so far indicates that the agent is a virus , the target tissue is muscle,
and the only known susceptible host is the rabbit.

Work has been suspended pending availability of space and technical support.



136



PHS-6040
(Rev. 10-76)



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Oo NOT use this space J



U.S. DEPARTMENT OF
HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



Z01-RS-00017-02 VR



PERIOD COVERED

October 1, 1977 to September 30, 1978

TITLE OF PROJECT (80 characters or less)



Experimental Atherosclerosis in Miniature Swine



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, ANO TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI: R. W. Mahley

D. L. Fry

R. L. Killens

D. K. Johnson

J . J . Knapka



Head, CAAMS
Chief, EA
Head, CMJ, VMSS
Chief, VMSS
Nutritionist, SAS



IR NHLBI
IR NHLBI
VRB DRS
VRB DRS
VRB DRS



COOPERATING UNITS (if any)

Laboratory of Experimental Atherosclerosis, NHLBI
Small Animal Section, -VRB, DRS



lab/branch

Veterinary Resources Branch



SECTION

Veterinary Medicine and Surgery Section



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, MD • 20014



TOTAL MANYEARS:



4.0



PROFESSIONAL:



2.0



2.0



CHECK APPROPRIATE BOX(ES)
□ (a) HUMAN SUBJECTS

D («1) MINORS □ (a2) INTERVIEWS



□ (b) HUMAN TISSUES



S (c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

To determine the effects of different kinds of dietary fats, with and without
cholesterol, on the pathogenesis of atherosclerosis using miniature swine as an
animal model for human disease. Experimental atherosclerosis in miniature
swine provides a model system for studying the interrelationships of dietary
and biochemical factors germane to the basic causes and mechanism of athero-
sclerosis.



137



PHS-6040
(Rev. 10-76)



Z01-RS-00017-02 VR

Objectives : To determine the effects of different kinds of dietary fats,
with and without cholesterol, on the pathogenesis of atherosclerosis.

Methods Employed : Fifty miniature swine of uniform age and size and equal sex
distribution were obtained. After baseline blood chemistry studies, the
animals were divided into groups receiving the following supplements to a
defined swine diet: tallow, tallow with 1.5 percent cholesterol, tallow with
1.5 percent cholesterol plus 0.75 percent taurocholic acid; lard, lard
with 1.5 percent cholesterol, lard with 1.5 percent cholesterol plus 0.75
percent taurocholic acid; cottonseed oil, cottonseed oil with 1.5 percent
cholesterol. The swine were kept on the diet for six months. Blood chemistry
was studied and animal weights determined weekly. Monthly serum samples were
collected for isolation and measurement of specific lipoproteins .

Ma j or Findings : Atherosclerosis was induced in swine fed the cholesterol
diets. The degree and extent of the disease correlated with the level of
total serum cholesterol. Significant findings were (l) thrombosis of the
following arteries: basilar, cerebral, anterior descending coronary, and
posterior descending coronary and (2) atherosclerosis with midrange serum
cholesterol levels. In both distribution and appearance, the lesions resembled
the disease in humans.

Significance : Detailed investigation of induced atherosclerosis in animal
models such as miniature swine is needed to explore the underlying causes and
progression of the disease. Atherosclerosis is a major disease of human
beings, a leading cause of death, and a debilitating condition affecting all
ages. The ability to produce the lesions in a reliable, reproducible manner
permits evaluation of a variety of parameters.

Proposed Course: Study is completed and data is being analyzed for publication.



138



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
HEALTH. EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl-RS-00018-03 VR



PERIOD COVERED

October 1, 1977 to September 30, 1978



TITLE OF PROJECT (80 characters or less)

The Pathogenesis of Chondrodysplasia in the Alaskan Malamute



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI:



M. Young
L. Killens
M. Ward
Prieur
Guarino



Acting Head, PS LT NCI

Head, CMU, VMSS VRB DRS

Veterinary Pathologist LT NCI

Pathologist LT NCI

Head, Toxicology LT NCI



COOPERATING UNITS (if any)

Laboratory of Toxicology, National Cancer Institute



LAB/ BRANCH

Veterinary Resources Branch



SECTION

Veterinary Medicine and Surgery Section



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, MP ' 20014



TOTAL MANYEARS:

1.0



PROFESSIONAL:

0.5



OTHER:



0.5



CHECK APPROPRIATE BOX(ES)
D (a) HUMAN SUBJECTS

D (al) MINORS □ (a2) INTERVIEWS



□ (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

The Alaskan malamute has naturally occurring chondrodysplasia , an inborn error
of metabolism that appears as a recessive trait with varying degrees of



expression. The animal serves as a useful model for studying the pathogenesis
of chondrodysplasia. Observation of growth patterns in puppies is especially
useful. Studies of biochemical, histochemical, and morphological changes serve
to define the disease in human beings. They may also elucidate mechanisms of
pathogenic processes that occur with neoplasms of the skeletal system.



PHS-6040



139



Z01-RS-00018-03 VR

Objectives : To elucidate the pathogenesis of chondrodysplasia in the Alaskan
malamute and compare these findings with those reported in man to determine if
the skeletal disorder in the malamutes is a good model for chondrodysplasia
dwarfism in man.

Methods Employed : A colony of ten Alaskan malamutes has been acquired. The
dogs are mated and all offspring are radiographed at established intervals to
detect early change and growth patterns indicative of chondrodysplasia.
Currently, the main emphasis is on repeated breeding and evaluation of bitches
and studs to obtain an increased number of puppies with the defect. Also,
another colony of malamutes is being established to permit collection of
additional baseline data.

Major Findings : The conception rates were very low during the year due to
immature studs. A method of artificial insemination was implemented to
induce pregnancy and to increase the number of pregnancies.

Significance : Cellular changes in cartilage and bone that accompany
chondrodysplasia can be studied in the Alaskan malamute. Identification of
morphological and biochemical alterations in animals with the disease elucidate
cellular defects that occur with other diseases that affect bone and cartilage
such as osteosarcoma.

Proposed Course: Continuation.



C



HO



I Lnoc mrunitmiun tAUlAMVit



jm i i noun i an ouitnut i w unmn i i un uaummu
PROJECT NUMBER (Oo NOT use this space;



...o. utrflKimtni ur PROJECT NUMBER

HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT h;01 RS 00019-02 VR



PERIOD COVERED

October 1, 1977 to September 30, 1978



TITLE OF PROJECT (80 characters or less)

Aging Studies on HSR, HSR-Stroke Prone, and WKY 'Rats



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT

PI: G. L. Clarke Veterinary Pathologist CPS VRB DRS

OTHER: S. Potkay Chief, SAS SAS VRB DRS

C. T. Hansen Geneticist _ SAS VRB DRS



COOPERATING UNITS (if any)

None



lab/branch

Veterinary Resources Branch



SECTION

Comparative Pathology Section



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, Maryland 20014



TOTAL MANYEARS:
0.7



PROFESSIONAL:

0.2



OTHERj

0.5



CHECK APPROPRIATE BOX(ES)
Q (a) HUMAN SUBJECTS

D (al) MINORS D (a2) INTERVIEWS



D (b) HUMAN TISSUES



3 (c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

The objective is to determine the nature and incidence of pathologic lesions
that develop throughout the lifespan of HSR, HSR-stroke prone , and WKY rats .
In each strain, 100 animals of both sexes will be selected for long-term holding.
Some subjects will be killed at the following ages: 2 months, 8 months,
12 months, 15 months, 18 months, 21 months, and 28 months. Tissues will be
studied by light microscopic methods, and if indicated, electron microscopic
techniques. These strains have great potential as animal models for the
study of cerebrovascular and hypertensive disease, in human beings. Their
value depends on accurate pathological description and documentation. In each
strain, 100 animals of both sexes will be selected for long-term holding.



141



PHS-6040
(Rev. 10-76)



i



Z01 RS 00019-02 VR

Objectives : To determine the nature and incidence of pathologic lesions that
develop throughout the lifespan of HSR, HSR- stroke prone, and WKY rats. HSR
rats are reported to be hypertensive, +14-0 mm Hg, but a pathologic study of
the strain apparently has not been made. The HSR-stroke prone rat is
reported to spontaneously develop cerebral infarcts, although documentation
is sketchy. The WKY is the parent strain of the HSR and HSR-stroke prone
rat and will be studied as a control.

Methods Employed : One hundred animals of each sex/strain will be selected
for long-term holding. Some subjects will be killed at the following ages:
2 months, 8 months, 12 months, 15 months, 18 months, 21 months, 24- months,
and 28 months. Tissues will be studied by light microscopic methods, and if
indicated, electron microscopic techniques.

S ignificance : These strains have great potential as animal models for the
study of cerebrovascular and hypertensive disease in humans. Their value
depends on accurate pathological description and documentation and will have
been established if correlation between the disease in the animals and human
beings is good.

Proposed Course: Continuation. To date the animals have not been received.



142



PROJECT NUMBER (Oo NOT use thlaH^



UMANUt

ace)



U. '. ULrAKlMtNT OF
HEALTH, EDUCATION, ANO WELFARE
PUPI.IC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



Z01-RS-00020-02 VR



PERIOD COVERED-

October 1, 1977 to September 30, 1978



TITLE OF PROJECT (80 characters or less)

Intrautero Injection of Herpes saimiri and Epstein- Barr Virus in
Pregnant Guinea Pigs



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, ANO TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT

LRTV NCI



PI: John W. Pearson
John D. Bacher



Head, VIS
Head, SU, VMSS



VRB DRS



'*jrr



COOPERATING UNITS (if any)

C. Lingeman, TPB, NCI
J. Hunter, BGY, NCI •

D. Twardzik, VO, NCI



LAB/ BRANCH

Veterinary Resources Branch



SECTION

Veterinary Medicine and Surgery Section



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, Maryland 20014



TOTAL MANYEARSt



.3



PROFESSIONALS

.2



OTHERt



.1



CHECK APPROPRIATE BOX(ES)
D (») HUMAN SUBJECTS ■

D («1) MINORS D (a 2 ) INTERVIEWS



□ (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

All serum samples from 12 guinea pigs infected as weanlings via different
routes of inoculation contained Viral Capsul Antigen (VCA) serum antibodies
to Epstein Barr Virus (EBV) with titers ranging from 1:10 to 1:40 over a
period of one year"! No Early Antigen (EA) serum antibodies have been
detected during this period. Fifteen animals inoculated intrautero or in
the bone marrow with EBV have shown VCA serum antibodies (1:20 to 1:80) and,
more important, nine revealed EA antibody to EBV, with titers ranging from
1:10 to 1:80 as judged by indirect immunofluorescence. Sera obtained from
four of seven animals injected intrautero with Herpes eaimiri (HVS) had
antibodies of both VCA (1:20 to 1:80) and EA (1:10 to 1:20).



143



PHS-6040
(Rtv. 10-76)



Z01-RS-00020-02 VR

Objectives: The aim of this project is to study two primate oncogenic viruses,
Epstein-Bare* (EBV) and Herpes saimiri (HVS), with regard to infectivity and
their transforming potential in vivo in guinea pigs and in various
populations of guinea pig cells. In vitro techniques have been employed to
follow vial infection based on antibody responses in guinea pigs inoculated
with EBV or HVS.

Methods Employed :

1. Inoculation of fetal guinea pigs (20 to 40 days gestation) with EBV and
HSV.

2. Inoculation of the same guinea pigs after birth with EBV and HSV.

3. Inoculation into the bone marrow of newborn guinea pigs.

4. Treatment of guinea pigs with guinea pig antithymus serum or drug
suppressive therapy before inoculation of animals with either EBV or HVS.

5. Use of indirect immunofluorescence to monitor guinea pigs infected with
EBV and HVS for humoral antibodies against associated antigens.

Major Findings : Eight guinea pigs injected intrautero with EBV followed by
six weekly injections after birth have been under observation for three months.
At two months, all animals exhibited Viral Capsule Antigen (VCA) serum anti-
bodies (1:20 to 1:80), and recently five of eight animals revealed Early
Antigen (EA) serum antibodies, with titers ranging from 1:10 to 1:80. So far,
peripheral blood smears are normal. After inoculation of EBV (10^*^ TU) into
the bone marrow of newborn guinea pigs, all animals have serum antibodies
to VCA, with titers ranging from 1:40 to greater than or equal to 1:80 as well
as antibody to the EA antigen (1:20). These animals have been studied only
six weeks and are being closely observed for signs of neoplasia.

Approximately three months ago, studies were undertaken to attempt to infect
guinea pigs with HVS. Seven animals were injected intrautero with approximately
10- 5 TCID/^Q! S , followed by six weekly injections of virus beginning after
birth. Two weeks after the last injection of virus, sera samples were taken
and checked for serum antibodies against HVS via indirect immunofluorescence.
Four of the guinea pigs exhibited VCA serum antibodies (1:20 to 1:80) when
tested against owl monkey kidney cells infected with HVS. Three of the four
animals positive for VCA antibody have exhibited EA serum antibody titers
ranging from 1:10 to 1:20. Peripheral blood smears obtained from these three
animals have remained normal. Because of the presence of EA antibody and
subsequent occurrence of lymphomas in the primate model, the animals are being
closely monitored for physical signs of neoplasia. Another four guinea pigs
with HVS injected into the bone marrow at birth have all shown VCA antibody
with titers ranging from 1:20 to 1:80. One of the four infected pigs has
shown an EA titer of 1:10. Again, all peripheral blood smears have remained
normal .



144



Z01-RS-00020-02 VR

Significance : The long-term goal of this project is to develop a guinea pig
model to study EBV, a virus implicated in human cancer, and HVS, a virus known
to transform human cells in vitro. Such a model system could provide evidence
of the involvement of these two herpes viruses in the pathogenesis of neoplasia
and serve as a definitive model for investigating measures for prevention and
treatment of cancer in human beings.

Proposed Course: The previously inoculated guinea pigs will be observed for the
development of neoplasia. In addition, newborn guinea pigs immunosuppressed
by removal of the cervical thymus will be inoculated with EBV and HVS.



145



SMITHSONIAN SCIENCE INFORMATION EXCMAN
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



Z01-RS-00022-02 VR



I



PERIOD COVERED '

Octbber 1, 1977 to September 30, 1978



TITLE OF PROJECT (80 characters or less)

Skeletal Age Development in Macaca mulatta



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT

PI:



M.


Michejda


Comparative Anatomist,


VMSS


VRB DRS


W.


Watson


Head, PRU, VMSS




VRB DRS


R.


L. Killens


Head, CMU, VMSS




VRB DRS


J.


D. Bacher


Head, SU, VMSS




VRB DRS


N.


R. Hayes


Deputy Chief, VMSS




VRB DRS


D.


K. Johnson


Chief, VMSS




VRB DRS



COOPERATING UNITS (if any)

N



lab/branch

Veterinary Resources Branch



SECTION

Veterinary Medicine and Surgery Section



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, MD '20014



TOTAL MANYEARS:



4.0



PROFESSIONAL:



3.0



OTHER:



1.0



CHECK APPROPRIATE BOX(ES)
□ (a) HUMAN SUBJECTS

D (al) MINORS □ (a2) INTERVIEWS



□ (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words t>r less - underline keywords)

The most widely used methods (dental age, body weight) for age estimation in
nonhuman primates are inadequate. More precise standards and age indicators are



needed and can be obtained by measuring skeletal age, which has proven to be the
the best criterion for assessment of chronological age. Our longitudinal radio-
graphic studies will provide information on the development and bone maturation
of the hand and wrist in Macaca mulatta monkeys. The data will cover the entire
period of appendicular bone maturation, from 120 days of gestation (the onset of
carpal center ossification) to adulthood (over five years). To obtain the fetal
data, a novel surgical technique of multiple uterotomies was developed. Serial
radiographic data are obtained at three uterotomies and after delivery. The
pre- and postnatal age indicators will be prepared for publication as an atlas,
which should make the data readily usable in many studies where the precise age
of the experimental animal is required.



146



PHS-6040
(Rev. 10-76)



Z01-RS-00022-02 VR

Objectives: To provide information on bone development and maturation of the
hand and wrist in the rhesus monkey, Macaca mulatta . This information will be
used for publication as an atlas and will serve as a comparison with human bone
maturation.

Methods Employed: Longitudinal radiographic study of ossification centers in
the hand and wrist of Macaca mulatta is being carried out in two age groups
(30 animals each) to assess skeletal age. The first group was initially
examined at 120 days of gestation, corresponding to the skeletal maturation
of human newborns, and studies of the second group were started at 127 days
of gestation. In the first group, uterotomies were performed and radiographic
data were obtained every two weeks at 120, 134, 148, and 162 days of gestation.
The last data were usually taken on neonates. In similar fashion, the second
group provided data on alternative weeks at 127, 141, 155 days of gestation.
The need for the two groups was necessitated by the surgical procedure and
the rapid rate of growth changes, particularly in the ossification centers
of the wrist, during the second trimester of fetal life. The pregnant
animals would not have tolerated weekly surgery, but staggering of the two
groups provided the necessary radiographic data on a weekly basis. During
the uterotomies ; the left hand of the fetus was temporarily removed from the
uterus and radiographed. The uniform dorsopalmar projection was applied at
a constant 40-cm tube-to-target distance. X-ray cassettes with intensifying
Du Pont screens were used to reduce exposure time to a minimum (1/30 sec,
40 KV, 30 mA). Each radiograph was analyzed to assess onset and status of
the ossification centers in the wrist and hand. The prenatal data will be
incorporated with existing logitudinal postnatal data. Complete information
about all stages of bone maturation and development in the hand and wrist
of M. mulatta will be evaluated in five age groups: prenatal, neonatal,
infant, juvenile, and adult.

Major Findings: Our longitudinal radiographic studies have shown characteristic
growth patterns of carpal ossification centers on a weekly basis. No radio-
graphic signs of carpal ossification centers were observed before 120 days of
gestation. Between 120 to 127 days of gestation, the onset of ossification
of radial epiphyses was observed. The ossification of one carpal bone per


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