Some publications by Donald S. Fredrickson 
  on research related to plasma lipids and lipoproteins
                    (Annotated by the author)

YR[1954. .
AU[ Fredrickson DS, AV Loud, BT Hinkleman, HS Schneider and ID
Frantz.
TI[ The effect of ligation of the common bile duct on cholesterol
synthesis in the rat.]
SO[ J Exp Med 99 (1954):43-53.]
NOTE[ First paper in the lipid field, work done during two years
in the laboratories of Ivan Frantz at the Massachusetts General
Hospital, prior to coming to the NIH. Ligation of the common bile
duct enormously increased the rate of synthesis of cholesterol by
the liver. The controlling effect of secretion of bile acids as
the  product of hepatic cholesterol synthesis was later shown by
Bergstr”m and co-workers in Sweden and Siperstein in Berkeley...

YR[1956
AU[ D.S. Fredrickson
TI[ The conversion of cholesterol-C14 to acids and other products
by liver mitochondria.
SO[ J. Biol Chem 222:109-120,1956. 

YR[1956
AU[ Fredrickson, D.S. And Ono, K. 
TI[ The in vitro production of 25-and 26-hydroxycholesterol and
their in-vivo metabolism.
SO[ Biochim. Biophys. Acta 22: 1183-184, 1956.

YR[1956
AU[ Steinberg, D and Fredrickson, D.S.
TI[ Inhibitors of cholesterol biosynthesis and the problem of
hypercholesterolemia.
SO[ Ann. N.Y. Acad. Sci 64:579-589, 1956.

YR[  1956. .
AU[  Havel RJ and DS Fredrickson.
TI[  The metabolism of chylomicra. I. The removal of palmitic
acid-C14 labeled chylomicra from dog plasma.]
SO[  J Clin Invest 35 (1956):1025-1032.]
NOTE[ The first study of the disappearance rate of chylomicron
TG,
revealing rapid reappearance of the labeled fatty acids in FFA.




YR[1957
AU[ Horning, M.G., Fredrickson, D.S. And Anfinsen, C.B.
TI[ Studies on enzymatic degradation of the cholesterol side-chain.II. Requirements of the mitochondrial system.
SO[ Arch. Biochem. Biophys. 71:266-273, 1957.

R[  1957. .
AU[  Fredrickson DS.
TI[  Some biochemical aspects of lipid and lipoprotein
metabolism.]
SO[  JAMA 164 (1957):1895-1899.]
NOTE[  This was my first (jejune) review article on lipoproteins
written for a symposium in New Orleans.  Among the participants
were Ancel Keys, Alistair Frazier from Birmingham, England, and
Emmett Holt Jr. John Youmans, now a medical school dean who had
grown up in the city as a cabaret trumpter, took us to see the
Vieux Carre. After we ran up a horrendous bill for colored water
for the bar-girls, Youmans led us out without paying,pursued by
the girls and bartenders.]


YR[ 1958
AU[Steinberg, D., Fredrickson, D.S. And Avigan, J.
TI[ Effects of   cholesterone in animals and man.
SO[ Proc. Soc. Exper. Biol. Med. 97: 784-790, 1958.
     [The adrenals of the animals increased markedly in size. The
     reason for this was apparent in the next paper.]

YR[ 1958
AU[ Fredrickson, D.S., Peterson, R.E. And Steinberg,D.
TI[ Adrenocortical steroid secretion by delta-4-cholesterone.
SO[ Science 127: 704-705, 1958.


YR[  1958. .
AU[  Fredrickson DS and RS Gordon Jr.
TI[  The metabolism of albumin-bound C14-labeled unesterified
fatty acids in normal human subjects
SO[  J Clin Invest 37 (1958):1504-1515.]
NOTE[   Bob Gordon and V.P. Dole of the Rockefeller Institute 
pioneered in discovering the plasma free fatty acids.  Bob called
them UFA and Dole, NEFA, The editor of J. Lipid Research
compromised with the term free fatty acids ("FFA"); imprecise
because they weren't free, but bound to albumin.) In this study
Gordon and I confirmed other evidence that turover of these
moieties in plasma was extremely rapid and represented a key
rapid transit system for readily available fat.]

YR[  1958. .
AU[  Fredrickson DS and RS Gordon Jr.
TI[  Transport of fatty acids.
SO[  Physiol Rev 38 (1958):585-630.]
NOTE[  Chris Anfinsen gave Gordon and me, both novitiates,
opportunity to write an authoritative review of FFA and emerging
knowledge about the biological nature of plasma lipoproteins.]

YR[  1959. .
AU[  Rodbell M and DS Fredrickson.
TI[  The nature of the proteins associated with dog and human
cylomicrons.]
SO[  J Biol Chem 234 (1959):562-571.]
NOTE[  Rodbell had earlier placed human chylo and VLDL proteins
on
urea-soaked starch gel blocks in order to get enough for the
determination of N-terminal amino acids of the apolipoproteins
carrying the loads of fat. He found evidence that there were
several proteins VLDL other than the accepted A and B proteins. 
We then teamed up to do obtain dog chylomicrons. We found
evidence of A and B proteins in the proteins from the
chylomicrons, along with another protein with a different
fingerprint.  This we called "C". (I think it may have been apoE,
not to be discovered for another decade.], 

YR[  1960. .
AU[  Fredrickson DS.
TI[  Essential Familial Hyperlipidemia. Chap. 16. In The
Metabolic Basis of Inherited Disease. First Edition. Edited by JB
Stanbury, JB Wyngaarden and DS Fredrickson.  (New York) McGraw
Hill, 1960. pp 489-552.]
NOTE[ This was the first edition of five editions of the book
which the editors dared to put together as the first real up-date
of Garrod's hallowed description of the inborn errors of
metabolism in 1908.]   

YR[  1961. .
AU[  Fredrickson DS, PH Altrocchi, LV Avioli, DS Goodman and
     HC Goodman.]
TI[  Tangier Disease.]
SO[  Ann Intern Med 55 (1961):1016.]
NOTE[  This is the first published report of Tangier Disease,  
reported earlier at a meeting on Lipidoses.  LV Avioli had been
referred the case by the Armed Forces Institute as a case of
"Niemann-Pick Disease."  When I told Avioli that his patient did
t not have NPD, I accepted his referral and founda low HDL and
widespread cholesteryl ester storage, We called it  Tangier
Disease,"for the island home in the Chesapeake Bay of the first
patients.].

YR[  1963. .
AU[  Fredrickson DS.
TI[  Newly recognized disorders of cholesterol metabolism.
SO[  Ann Intern. Med. 58 (1963):718.]
NOTE[ The first brief description of Lola Mc, whom I first called
"hepatic cholesterol ester storage disease. Later Schiff et al.
pointed out that the disease was widespread and the name
"cholesterol ester storage disease" was therefore adopted by us
all. Sloan and I later discovered that the disorder was due to
heritable deficiency of cholesteryl ester hydrolase (acid
lipase). Wolman's disease was the allotype in infants.]

AU[   Fredrickson DS, K Ono and LL Davis.
TI[  Lipolytic activity of post-heparin plasma in
hypertriglyceridemia.]
SO[  J Lipid Res 4 (1963):24-33.]
NOTE[Havel and Gordon had first noted that one of our Type I
families was deficient in lipoprotein lipase after intravenous
heparin. In this study we concluded that we were having to cope
with more than one lipase. Scores of studies of  LPL" in man were
discounted because of the presence of still unknown hepatic
lipase.]

YR[  1964. .
AU[  Fredrickson DS.
TI[  The inheritance of high density lipoprotein deficiency.
(Tangier disease.)
SO[  J Clin Invest 43 (1964):228.]
NOTE[  After working up T. L. we made a trip to Tangier Island
where the mother, showed me his sister's tonsils.  When I saw
those gigantic bright orange organs, I had the same feeling one
gets at looking at a mountain that has never been climbed.  This
paper was the product of numerous trips to the island to
reconstruct the history of this family for six generations
through the memory of Mrs. Nettie Crockett Pruitt, former school
teacher.  The island records had been destroyed by an early
Methodist preacher.  Using low HDL as a marker, we showed this to
be an autosomal recessive condition. By 1980 about 30 cases had
been discovered elsewhere.]

YR[  1965. .
AU[  Fredrickson DS and RI Levy.
TI[  A functional view of the plasma lipoproteins.]
SO[  In Lipoide (Colloquium der Gesselschaft fur physiologische
Chemie, Mosbach, Germany, April, 1965. E. Schutte, Ed.
Springer-Verlag, Stuttgart, 1966.  pp. 124-139.
NOTE[Invited by Professor Ernst Klenk (K”ln) to allow me to
defend my growing belief in the specificity of the still
evanecent apolipoproteins. Many of the German professors of
physiological chemistry were there.  Afterward Willy Stoffel,
Klenk's docent and later his successor, leaned over and said to
me "You did very well, but they don't believe a thing you said".]


YR[  1965. .
AU[  Fredrickson DS and RS Lees.
TI[  A system for phenotyping hyperlipoproteinemia.]
SO[  Circulation 31 (1965):321-327.]
NOTE[ First report of a different kind of Type III, the "broad
beta" syndrome with tubereruptive xanthomas.]

YR[  1966 . .
AU[  Levy RI, RS Lees and DS Fredrickson.
TI[  Nature of prebeta (very low density) lipoproteins.
SO[  J. clin Investigation. 45 (1966):63-77.]
NOTE[ The beginning of a clearer definition of Type III.] 

@Book
YR[ 1966 . .
AU[ Fredrickson DS and RS Lees.
TI[ Familial Hyperlipoproteinemia. Chapter 22. In The Metabolic
Basis of Inherited Disease. Second Edition.
IM[ (New York) McGraw-Hill, 1966. pp 429-488.]
NOTE[ By this time,as many as four familial syndromes of
"essential hyperlipoproteinemia" can be distinguished.This was
the first time that type V appeared as a distinct syndrome.
We were running a breathless race evolving a system as we
attempted to write a textbook, and I regret that we were
sometimes publishing material here for the first time.]

YR[ 1967. .
AU[ Fredrickson DS, RI Levy and RS Lees.
TI[ Fat transport in lipoproteins--an integrated approach to
mechanisms and disorders.]
SO[ N Engl J Med 276
(1967):32-44,94-103,148-156,215-226,273-281.]
NOTE[The definitive review for the time.]  .

YR[ 1969. .
AU[ Fredrickson DS, RI Levy and FT Lindgren.
TI[ A comparison of heritable abnormal lipoprotein patterns
as defined by two different techniques.]
SO[ J clin Invest 47 (1969):2446-57.]
NOTE[ We checked to be sure that the centrifuge patterns in a
patient with Type III were identical to those earlier reported by
Gofman in patients with  xanthoma tuberosum".]

YR[ 1969. .
AU[ Brown WV, RI Levy and DS Fredrickson.
TI[ Studies of the proteins in human plasma very low density
lipoproteins.]
SO[ J Biol Chem 244 (1969):5687-94.]

YR[ 1970. .
AU[ Brown WV, RI Levy and DS Fredrickson.
TI[ Further characterization of apolipoproteins from the human
plasma very low density lipoproteins.]
SO[ J Biol Chem 245 (1970):6588-94.]

YR[ 1970. .
AU[ Brown WV, RI Levy and DS Fredrickson.
TI[ Further separation of the apoproteins of the human plasma
very low density lipoproteins.]
SO[ Biochim Biophys Acta 200 (1970):573-5.]
NOTE[The above three papers describe the discovery and isolation
of the Apoproteins C-I, C-II and CIII from human plasma.]


YR[  1970. .
AU[  Fredrickson DS, RI Levy, E Jones, M Bonnell and N Ernst.
TI[  The Dietary Management of Hyperlipoproteinemia: A Handbook
for Physicians.]
SO[  U.S. Department of Health, Education and Welfare, Public
Health Service,
U. S. Government Printing Office, Washington, D.C., 1970.]
NOTE[  This is the first of the printings of the diet books. 
Prepared for the treatment of the five phenotypes. Over 7 million
were supplied to requesting physicians.]

YR[  1970 . .
AU[  LaRosa JC, RI Levy, WV Brown and DS Fredrickson.
TI[  A specific apoprotein activator for lipoprotein lipase.]
SO[  Biochem Biophys Comun 41 (1970):57-62.]
NOTE[  This is a co-discovery,  Havel, the Shores, and Fielding,
published simultaneously in 1971 that apolipoprotein C-II.was the 
 activator" reported by Anfinsen, Boyle and Brown in 1952.]

YR[  1970 . .
AU[  Beaumont JL, LA Carlson, GR Cooper, Z Fajfar, DS Fredrickson
  and T Strasser.
TI[  Classification of hyperlipidaemias and
hyperlipoproteinemias.]
SO[  Bull  Wld Hlth Org 43 (1970):891-915.]
NOTE[  An "international pact" was worked out in a humid week in
Geneva.  The decision to make our system an international
"standard" for lipoprotein phenotyping initially met a good deal
of resistance from Beaumont (who thought that all hyperlipidemia
was likely due to immunological abnormality) and Lars Carlson.I
later visited the latter in Stockholm and found his young men
assiduously  reading the wash."(electrophoretic strips.]

YR[  1970. .
AU[  Fredrickson DS Chairman.
TI[  Report of the National Heart and Lung Institute Panel on
Hyperlipidemia and Premature Atherosclerosis. June 12-13, 1970.]
SO[  National Heart and Lung Institute, DHEW. 1970.]
NOTE[ This was a meeting of 20 participants and seven observers
convened by Theodore Cooper director of NHLI.which led to the
establishment of the nationwide Lipid Research Clincs.

YR[ 1972. .
AU[ Fredrickson DS, SE Lux and PN Herbert.
TI[ The apolipoproteins.]
SO[ Adv Exp Med Biol 26 (1972):25-56.]
NOTE[ A paper describing the naming of apolipoproteins in the
1960s.  The three biggest hunters at the time were the Shores in
Berkeley, Alaupovic in Oklahoma City and ourselves."The naming of
something that is new but whose individuality emerges slowly is
always a problem.  Sometimes a trivial name is born of early
inspiration and survives well.  With complex chemical
substances,the idiom often evolves parallel with technique, and
multiple designations arise, each with its own champion.
      In the earliest convention, aproprotein A, or apoA and
apoprotein B or apoB,referred to the major apoproteins found in
HDL and LDL,respectively. Beginning in 1968, Alaupovic and co-workers proposed that each of the polypeptides belongs in one of
three or more corporate groups that had functional relationships
and presumably common (genetic) origin, hence the ABC system. .
     C-terminal Nomenclature. The Shores and we preferred to use
the C-terminal residue as the name-tag for each protein, i.e.
R-ala,or apoLP-ala or apoHDL-ala . The system was open-ended and
without presumption of functional relationships to other
apoproteins.. The weakest feature of the C-terminal system was
the determination of the residues themselves and the possible
occurrence of the same terminal residue in different proteins.
Significant errors had already been made . I decided that we
should give way to the  simpler" system .despite misgivings about
unproved assumptions of genetic linkage and "quartenary"
relationships. I sent Peter Herbert to a meeting in Austria at
which time he announced the concession.  I thought of it later as
the Concordance of Graz.]

R[ 1972. .
AU[ Sloan HR and DS Fredrickson.
TI[ The enzyme deficiency in cholesteryl ester storage disease.]
S0[ J Clin Invest 51 (1972):1923-6.]


YR[1972. .
AU[Friedewald WT, RI Levy and DS Fredrickson.
TI[ Estimation of the concentration of low-density lipoprotein
cholesterol in plasma, without use of the preparative
ultracentrifuge.]
SO[  Clin. Chem. 18 (1972):499-502.
NOTE[  The origin of the "Friedewald Formula", still used around
the world, We had observed that this rule: [LDLC = PlasmaC -
(HDLC + TG/5, provided Type III excluded] would work, but we
wanted a good statistician to be sure. Bill Friedewald was the
NIH  biometrician who agreed to do the math.]


YR[ 1972. .
AU[ LaRosa JC, RI Levy, HG Windmueller and DS Fredrickson.
TI[ Comparison of the triglyceride lipase of liver, adipose
tissue, and postheparin plasma.]
SO[ J Lipid Res 13 (1972):356-63.]
NOTE[Here emerges hepatic lipase.Multiple groups were now finding
multiple lipases after heparin.}

YR[ 1974. .
AU[ Krauss RM, RI Levy and DS Fredrickson.
TI[ Selective measurement of two lipase activities in postheparin
plasma from normal subjects and patients with hyper-
lipoproteinemia.]
SO[ J Clin Invest 54 (1974):1107-24.]
NOTE[ For a few years the 'gold standard' for determining
lipoprotein lipase responses after heparin.]


YR[ 1975. .
AU[ Fredrickson DS.
TI[ It's time to be practical.]
SO[ Circulation 51 (1975):209-11.]
NOTE[ This was the abnegation of using electophoresis for
phenotyping hyperlipoproteinemia.  It had become a minor industry
among clinical laboratories around the world. The certain
ascertainiment required use of the preparative ultracentrifuge.] 

YR[1975
AU[ Fredrickson DS,  J Morganroth and RI Levy.
TI[ Type III hyperlipoproteinemia: an analysis of two
contemporary  definitions.]
SO[ Ann Intern Med 82 (1975):150-7.]
NOTE[ Proposal of a simple diagnosis of Type III based on easily
available clinical data.]


YR[  1978. .
AU[  Wade, N
TI[  Send not to know for whom the Nobel tolls: it's not for
thee.]
SO[  Science 202 (1978):295-296
NOTE[  See also Current Contents (July 10, 1978).  Wade includes
in his article names taken from a list of 300 most-cited authors
during 1961-1975, compiled by Eugene Garfield of the Institute of
Scientific Information.  Four categories are shown: Molecular
Biology, Endocrinoslogy, Cell Biology and Physiology. In the
latter category,the most cited physiologist was D.S.
Fredrickson.]

YR[1993
AU[ Fredrickson, Donald S.
TI[ Phenotyping: On reaching base camp (1950-1975)
SO[Circulation Supplement 87: No.. 4, III-1-15.
NOTE[ An invited lecture at the International Atherosclerosis
Society (the first of a triennial Fredrickson Lecture on
Lipoproteins) The inaugural talk was a summation of the
lipoprotein era (with particular emphasis on the Bethesda
contributions, from 1950 to the arrival of molecular biology.) 
We had reached base camp from which the ascent of the now visible 
high peaks could begin.]