Squalene in Human and Rat Blood Plasma*

Goodman, DeWitt S.

doi:10.1172/jci105024

Cited by 46 publications

(15 citation statements)

References 26 publications

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“…It was very stable despite important variations of glucocorticosteroid excretion, and work under progress in our laboratory confirms that even under maximal stimulation by corticotropin the dilution of the specific activity of hydrocortisone compared to plasma cholesterol does not exceed the figure of about 20%o. This dilution must represent the synthesis in situ directly from acetate or other unlabeled precursors (20). That the contribution of this local synthesis in man is independent of the importance of glucocorticosteroid production confirms the observations of Werbin and Chaikoff in the animal (8).'…”

Section: Discussionsupporting

confidence: 69%

Blood Cholesterol and Hydrocortisone Production in Man: Quantitative Aspects of the Utilization of Circulating Cholesterol by the Adrenals at Rest and under Adrenocorticotropin Stimulation*

Borkowski¹,

Levin²,

Delcroix³

et al. 1967

J. Clin. Invest.

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Summary. A kinetic study of the conversion of blood cholesterol into hydrocortisone was carried out in two patients through prolonged infusions of cholesterol-4-14C. The following points appear to be established by our observations:1) The infused tracer behaved metabolically like endogenous cholesterol; it could therefore serve as a means of labeling plasma cholesterol for investigating its utilization by the adrenal cortex.2) At rest, about 80% of hydrocortisone derived from plasma cholesterol, the other 20% thus being synthesized in situ from acetate and other unlabeled precursors.3) Under ACTH stimulation the participation of plasma cholesterol in the synthesis of hydrocortisone was the same as at rest; the conversion of plasma cholesterol into hydrocortisone was thus proportional to the production of glucocorticosteroids by the adrenal glands.4) The specific activities of hydrocortisone allowed us to trace its adrenal precursors including adrenal cholesterol. The kinetics of the replacement of adrenal cholesterol by plasma cholesterol underlined the functional heterogeneity of the former. The experimental data were compatible with the following model: A fraction of plasma cholesterol entering the adrenal cell is immediately available for metabolism and conversion into steroid hormones, and another fraction turns over slowly, representing some form of storage.

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Section: Discussionsupporting

confidence: 69%

Blood Cholesterol and Hydrocortisone Production in Man: Quantitative Aspects of the Utilization of Circulating Cholesterol by the Adrenals at Rest and under Adrenocorticotropin Stimulation*

Borkowski¹,

Levin²,

Delcroix³

et al. 1967

J. Clin. Invest.

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“…It seems not improbable, therefore, that the kidney may release a portion of these cholesterol precursors into the circulation to be carried to the liver, there finally to be converted to cholesterol. Goodman's finding that significant quantities of squalene are present in the blood of both man and rat lends some support to the likelihood of such an active circulating pool of squalene in these species (27).…”

Section: Discussionmentioning

confidence: 99%

Studies of the In Vivo Metabolism of Mevalonic Acid in the Normal Rat

Hellström¹,

Siperstein²,

Bricker³

et al. 1973

J. Clin. Invest.

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A B S T R A C T Studies were performed to examine synthesis, tissue localization, and metabolism of mevalonic acid in normal rats. Circulating mevalonate was found to have a rapid turnover phase of 5 min and a slower phase of 40-50 min. Under in vitro conditions the synthesis of mevalonate is carried out most actively by the liver and only to a minor extent by the other tissues studied. The most unexpected finding of this study was that both in vivo and in vitro the kidneys rather than the liver are the primary site of the metabolism of circulating mevalonate. Whereas mevalonate in the liver is rapidly transformed to cholesterol, the major products of mevalonate metabolism in the renal tissues during the same time period are squalene and lanosterol. Exogenous in contrast to circulating mevalonate is metabolized primarily in the intestine.

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“…Furthermore, the overwhelming majority of the peritoneal cells of irradiated repopulated animals are macrophages, as judged by their size and phagocytic activity (20). Immunological and chromosomal studies have established unequivocally that peritoneal (free) macrophages originate from precursor cells in the bone marrow, probably of monocytic type (16,18,(20)(21)(22)(23).…”

Section: Methodsmentioning

confidence: 99%

Tumor-Host Cell Hybrids in Radiochimeras

Wiener

Fenyõ

Klein

1974

Proc. Natl. Acad. Sci. U.S.A.

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F1 hybrid mice syngeneic or semiallogeneic with respect to the relevant tumor were lethally irradiated and then reconstituted with hemopoietic cells from strain CBAT6T6 mice. After chimerism had been established, the animals were inoculated with solid or ascites tumors. Tumor-host cell hybrids were selected from enzyme-deficient solid tumors by explanting the tumor cell suspension into hypoxanthine-amethopterin-thymidine containing medium. The selection of hybrid cells from ascites tumors was achieved by exploiting the difference between the ascites tumor cells and hybrid cells in their ability to adhere to the surface of culture vessels. T6T6 chromosomal and H-2 antigenic markers served to distinguish between the hemopoietic cells derived from the donor graft and the cells of the host. All solid tumors tested fused with cells of the irradiated host, whereas ascites tumors fused with repopulating cells ofhemopoietic origin.In two previous publications (1, 2) we have described the successful selective isolation of tumor-host cell hybrids from The type of host cell involved in the fusion is unknown. In order to assess the biological significance of the phenomenon, it was obviously important to define this, at least in outline. Radiation chimeras in which the host and the repopulating cells carried different markers appeared to present a possible approach to this question. MATERIALS AND METHODSThe experimental design was as follows. F1 hybrid mice syngeneic or semiallogeneic with respect to the test tumor were lethally irradiated and then reconstituted with CBAT6T6 hemopoietic cells. After chimerism had been established, the animals were inoculated with solid or ascites tumors. Tumor-host cell hybrids were selected as previously described (1, 2). T6T6 chromosomal and H-2 antigenic markers served to distinguish between the hemopoietic cells derived from the embryonic liver graft and the cells of the host.Production of Chimeras. C3H X DBA/2, C3H X C57B1, and C3H X C57 leaden F. hybrid mice, 6-8 weeks old, were lethally irradiated with 800 R (3). About 5 X 105 hemopoietic cells obtained from the liver of newborn CBAT6T6 mice were suspended in 0.5 ml of sterile Eagle's minimal essential medium and inoculated into the tail vein of an irradiated recipient. The development of chimerism was confirmed by examining metaphase plates of spleen or lymph node cells. As a rule, lymphopoietic and hemopoietic organs were repopulated with T6T6 marker positive cells within 2-3 weeks.Tumors. (a). Solid tumors. A9HT and B82HT are highly malignant variants selected from the L cell sublines, A9 and B82 (4). Like the original in vitro lines from which they were derived, A9HT and B82HT are enzyme-deficient; A9HT lacks hypoxanthinq -guanine -phosphoribosyltransferase (HGPRT), while B82HT lacks thymidine kinase (TK). Due to these enzyme deficiencies both lines are unable to grow on hypoxanthine-amethopterin-thymidine (HAT) medium. With inoculla of 4 X 104 to 4 X 104 cells, both lines grew progressively in newborn x-irradiated (4 J k...

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Squalene in Human and Rat Blood Plasma*

Cited by 46 publications

References 26 publications

Blood Cholesterol and Hydrocortisone Production in Man: Quantitative Aspects of the Utilization of Circulating Cholesterol by the Adrenals at Rest and under Adrenocorticotropin Stimulation*

Blood Cholesterol and Hydrocortisone Production in Man: Quantitative Aspects of the Utilization of Circulating Cholesterol by the Adrenals at Rest and under Adrenocorticotropin Stimulation*

Studies of the In Vivo Metabolism of Mevalonic Acid in the Normal Rat

Tumor-Host Cell Hybrids in Radiochimeras

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