PROPOSALS FOR PEDIATRIC RESEARCH PROJECTS

IN ROCKEFELLER UNIVERSITY HOSPITAL

I.  Role of Sulfur Amino Acid Hetabolism in Coronary Artery Disease.

   It is envisaged that this project would be done in collaboration with
Dr. Ahrens and would consist of direct enzymatic as well as in vivo metabolic
studies of methionine, cyst(e)lne and taurine.  Abnormal i tierompid and
carbohydrate metabol ism are more we1 1 known as risk factors for coronary
artery disease.  Recent work suggests that altered sulfur amino acid metabo-
lism may constitute an additional risk factor in genetically susceptible
individuals by contributing to the production of endothelial damage. It is
proposed to study patients who have a paucity of known risk factors. The
general approach would include direct enzymatic analysis of the enzymes of
sulfur metabolism In skin culture and long-term lymphoid cell lines as well
as in vivo loading tests with sulfur-containing amino acids.  My laboratory
hascomerable background and experience in both of these approaches,
although they have never been applied to this group of disorders.

II.  Inborn Errors of Amino Acid and Organic Acid Metabolism.

     This study would be a continuation of ongoing clinical, enzymatic and
  metabolic studies in patients with this group of inherited disorders.

Ill.  The Role of Taurine in Control of Bile Salt and Cholesterol Metabolism In Han.

   It is anticipated that this study also would be done in collaboration
with Dr. Ahrens' group.  Our group has shown that there is a nutritional re-
quirement for taurine in man.  The only known biochemical reaction which
taurine undergoes is the conjugation of bile acids. There is some evidence
that the conjugation of bile salts by taurine may be involved in the control
of cholesterol pool sizes and cholesterol synthesis. Taurine and cholesterol
are both present in large concentrations in human milk, but not in bovine
milk or the manufactured formulas derived from bovine milk. Study of these
interrelationships in infants, children and adults may be of considerable
general nutritional interest.

IV.  Transfer of Nutrients and Toxins in Human Milk.

  This project would involve the use of nursing mothers and direct
measurement of transfer to the infants of nutrients and possible toxins in
their milk.  The rototyplc compound used in the first instance would be
C13-taurine and N f S-labelled polyamines.  This project would involve gas
chromatography-mass spectrometry with the mass spectrometer being utilized
as a qualitative analytical as well as quantitative tool (mass fragmentography).


V.  Amino Acid and Protein Metabolism in Nutrition in Infants and Children.

  This project would also involve mass spectrometry and the use of
stable isotopes in determination of rates of synthesis, turnover rates and
body pools.  In children the use of radioisotopes is ethically unacceptable
and stable isotope techniques must be worked out to gain a more dynamic
view of protein requirements in amino acid metabolism during development.

VI.

Metabolic and Nutritional Studies of Anorexia Nervosa.

  Thls fascinating disorder is a voluntary restriction of food intake
which is seen mainly in adolescent young women although it is also seen
in adolescent boys.  There is no real anorexia but rather a voluntary
restriction of food intake which is generally assumed to be of psychogenic
origin.  Unlike lnvoluntary undernutrition, signs and symptoms of anemia,
vitamin, and protein deficiency are often lacking.  There is a paucity of
hard information about changes in body composition and the reasons why
the metabolic changes found in this disorder differ from those found in
involuntary food restriction.  It represents an interesting theoretical
model as well as an important pediatric problem.  It is envisaged that this
problem might be approached in collaboration with Dr. Jules Hirsch.