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L A Sauer

Publications and source records attributed to L A Sauer.

At least 37 records · Page 2Linked to original sources
PubMed1987

In vivo nutrient uptake by head and neck cancers.

The arteriovenous uptake differences for glucose, lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate were measured in vessels across squamous cell carcinomas in ten selected patients with tumors of the head and neck. All tumors measured took up glucose, pyruvate, beta-hydroxybutyrate, and acetoacetate. They could either produce, take up, or maintain a constant level of lactate. These tumors demonstrate a heterogeneous affinity for various metabolites, including ketone bodies which are elevated in the nutritionally depleted, tumor-burdened patient.

3-Hydroxybutyric Acid↗
PubMed1987

Stimulation of tumor growth in adult rats in vivo during acute streptozotocin-induced diabetes.

The effects of acute diabetes mellitus on the growth of Morris hepatoma 7288CTC and Jensen sarcoma were studied in fed, young (less than 200 g), and adult (greater than 250 g) rats. Animals were matched for tumor size and growth; the rates of tumor growth were the same in fed, young and adult nondiabetic rats. Diabetes was induced by the i.v. injection of streptozotocin (65 mg/kg total body weight) into tumor-bearing rats and changes in arterial blood nutrient concentrations were compared to changes in the rates of tumor growth and DNA synthesis. In young rats acute diabetes did not increase the blood concentrations of the fat store-derived nutrients and did not increase the rate of tumor growth. In adult rats, however, acute diabetes raised the arterial blood free fatty acid, glycerol, triglyceride, and ketone body concentrations to high levels and increased the rate of tumor growth about three times over that observed in untreated rats. Progress curves for the mobilization of host fat stores and for incorporation of [methyl-3H]thymidine into tumor DNA during the onset of diabetes showed that these activities were closely correlated in adult rats. Both processes began to increase 2 to 4 h after streptozotocin treatment, reached an initial peak at 12 to 16 h, decreased to a low point at 18 to 20 h, and then increased again to the new steady state after 23 to 24 h. The results indicate that the rate of tumor growth in rats in vivo is limited by the availability of a substance(s) present in the hyperlipemic blood of adult diabetic rats. The tight relationship between host lipolysis and tumor growth suggests that the substance(s) is derived from host fat stores.

Animals↗
PubMed1987

Blood nutrient concentrations and tumor growth in vivo in rats: relationships during the onset of an acute fast.

The rate of tumor growth in vivo in adult rats (250- to 350-g total body weight) is stimulated during an acute fast. No tumor growth stimulation is observed in fasted immature rats (less than about 200-g total body weight). The different tumor growth responses in rats of these two age groups appear to depend on the increased availability to the tumor of nutrients from host fat stores in adult rats. Immature rats, which lack significant fat stores, show neither hyperlipemia nor ketosis during fasting. These experiments were performed to determine the relationship between blood fat store-derived nutrient concentrations and the onset of stimulated tumor growth in fasted adult rats. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fast. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Mobilization of host fat stores leading to increased blood concentrations of free fatty acids, glycerol, ketone bodies, and triglycerides started about 7 h after food was removed and reached its maximum after about 15 h. Increased rates of tumor growth and incorporation of thymidine into tumor DNA correlated closely with the higher circulating nutrient concentrations. Both the nutrient concentrations and tumor growth were decreased by refeeding. These findings suggest that the availability of nutrients derived from host fat stores may be rate limiting for tumor growth in vivo.

Animals↗
PubMed1986

Stimulation of tumor growth in adult rats in vivo during an acute fast.

These experiments investigate an increase in tumor growth that occurs in adult rats in vivo during an acute fast. The effects of feeding, fasting, and underfeeding on the growth of Morris hepatomas 5123C and 7288CTC in Buffalo rats and of Walker carcinoma 256 and Jensen sarcoma in Sprague-Dawley rats were studied. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fasting or underfeeding. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Fasting increased the rate of growth of the tumors 3 to 4 times over that measured in fed rats. This effect began during the first day of fasting and ended abruptly on refeeding. After refeeding tumor growth slowed to the rate in fed rats. Tumors from fed or fasted rats were not different in cellularity or dry weight/g wet weight. A positive growth response in the tumor required lipolysis and ketosis in the host. No stimulation was observed during an acute fast in either immature rats or in mature rats whose weights had been reduced by underfeeding. These animals have small fat stores and show no increase in arterial blood free fatty acid or ketone body concentrations during an acute fast. Finally, underfeeding of adult rats raised the blood concentrations of these nutrients to values that were intermediate between those in fasted and fed rats. Tumor growth rates in these rats were intermediate between those in fasted and fed rats. The results support the proposal that an increase in availability of free fatty acids and/or ketone bodies is the stimulus that increases the rate of tumor growth during an acute fast.

Animals↗
PubMed1986

Preparation of "tissue-isolated" rat tumors for perfusion: a new surgical technique that preserves continuous blood flow.

A surgical technique for preparing "tissue-isolated" rat tumors for perfusion was developed that ensures continuous blood flow to the tissue. The tumor may be perfused in situ or ex vivo. Tumor venous blood flow, tumor glucose and lactic acid metabolism, as well as host animal respiration and core temperature, were unchanged during the procedure. Following addition of 14C-D-Glucose to the tumor afferent blood, all radioactivity appeared in the tumor venous blood. None appeared in the host systemic blood, indicating complete separation of tumor and host vasculature during in situ perfusion.

Animals↗
PubMed1986

In vivo lactate production and utilization by Jensen sarcoma and Morris hepatoma 7288CTC.

These experiments were designed to determine the characteristics of lactic acid utilization and production in vivo in Jensen sarcoma and Morris hepatoma 7288CTC. Arteriovenous differences for lactic and pyruvic acids, glucose, and the ketone bodies were measured across "tissue-isolated" tumors growing in fed and fasted rats. Lactic acid was utilized (n = 18), produced (n = 24), or neither utilized nor produced (n = 1) by the tumors. Net tumor lactate production or utilization did not depend on the mean rate of glucose utilization which was the same in the lactate-utilizing and -producing tumors. For the lactic acid-utilizing tumors, the mean arterial whole blood lactate concentration entering the tumor was 3.47 +/- 0.39 mM, and the concentration in the tumor venous blood was 2.31 +/- 0.25 mM. For the lactic acid-producing tumors, the mean arterial lactic acid concentration was 1.29 +/- 0.10 mM, and the tumor venous blood concentration was 2.19 +/- 0.19 mM. Thus, both lactate-producing and lactate-utilizing tumors showed identical rates of glucose utilization and identical lactic acid concentrations in the venous blood leaving the tumors. Metabolite levels were also measured in tumors that were freeze clamped in situ immediately following collection of the arterial and tumor venous blood samples. The lactic acid content in the tumor mass (corrected for total tumor water) and the concentration in the tumor venous blood plasma were nearly identical, suggesting that the lactate concentrations in the tumor cells and tumor venous blood are at equilibrium. Transport of lactic acid between arterial plasma and tumor or between tumor and venous plasma was always down a concentration gradient; net lactate uptake and release in these tumors followed the law of mass action. High lactate concentrations were not observed in the Jensen sarcomas or in the venous blood leaving these tumors, and we were unable to confirm earlier studies indicating that Jensen sarcomas are consistently high net lactate producers in vivo.

Animals↗
PubMed1985

Regulation of lactate production and utilization in rat tumors in vivo.

These experiments were performed to determine the factor(s) that regulate lactic acid production and utilization by rat tumors in vivo. Arteriovenous differences for glucose and lactic, pyruvic, 3-OH-butyric, and acetoacetic acids were measured across "tissue-isolated" Walker 256 sarcocarcinomas and Morris 5123C hepatomas in fasted rats anesthetized with sodium pentobarbital. Twenty-six per cent of the sarcocarcinomas (n = 53) and 48% of the hepatomas (n = 29) utilized blood lactic acid. The remainder released lactic acid into the venous blood. The steady-state rate of glucose consumption was similar in both lactate-producing and lactate-utilizing tumors. The range of lactate concentrations in the blood leaving the tumors was narrower than the range of lactate concentrations in the blood entering the tumors. This difference was caused by tumor lactic acid production at low arterial lactate concentrations and tumor lactic acid utilization at high arterial lactate concentrations. Individual tumors changed from lactic acid production to lactic acid utilization in a matter of minutes in response to an increase in the arterial lactic acid concentration. Mean lactic plus pyruvic acid concentrations and lactic/pyruvic acid ratios in the tumor venous blood were 2.15 +/- 0.22 and 23.4 +/- 3.7 mM, respectively, for Walker sarcocarcinoma 256 (n = 18) and 1.28 +/- 0.13 and 48.1 +/- 5.1 mM, respectively, for hepatoma 5123C (n = 11). The results suggest: that a steady-state lactic plus pyruvic acid concentration and lactic/pyruvic acid ratio are maintained in the tumor cell cytoplasm by the active glycolytic pathway and by lactic acid dehydrogenase; that the tumor intracellular concentrations equilibrate with the arterial blood and that the tumor steady state is expressed in the tumor venous blood; and that tumor lactic acid production or utilization results from the equilibration between the variable arterial lactic acid concentration and the more constant tumor intracellular steady-state lactic acid concentration. Since the arterial lactate concentration may be less than, greater than, or equal to the intracellular steady-state concentration, an individual tumor may produce, utilize or neither produce nor utilize lactic acid.

Animals↗
PubMed1983

Ketone body, glucose, lactic acid, and amino acid utilization by tumors in vivo in fasted rats.

Arteriovenous differences for acetoacetate, beta-hydroxybutyrate, glucose, lactic acid, and glutamine and other amino acids were measured across Morris hepatomas 5123C, 7777, and 7288CTCF and Walker sarcocarcinoma 256 in vivo in rats fasted for 2 days. The acetoacetate and beta-hydroxybutyrate concentrations in arterial whole blood of fasted tumor-bearing rats were 0.52 +/- 0.06 and 1.82 +/- 0.19 mM (S.E., n = 38), respectively. Both ketone bodies were utilized by the tumors, and the rates of utilization were directly related to the rates of supply. The mean utilization rates for acetoacetate and beta-hydroxybutyrate were 13.9 +/- 2.9 (range, 0 to 64; n = 30) and 24.7 +/- 4.4 (range, 0 to 145; n = 38) nmol/min/g tumor wet weight, respectively. Eight of the tumors produced acetoacetate, presumably from utilized beta-hydroxybutyrate. An average of 52% of the acetoacetate and 30% of the beta-hydroxybutyrate carried in the arterial blood was removed during one pass through the tumors. The concentrations of glucose and glutamine in the arterial whole blood of fasted tumor-bearing rats (n = 38) were 6.55 +/- 0.3 and 0.76 +/- 0.02 mM, respectively; both of these substrates were utilized at rates that were directly proportional to the rates of supply. The mean rates of glucose and glutamine utilization for all tumors in fasted rats were 101 +/- 11 (range, 3 to 313) and 8.2 +/- 1.1 (range, 0 to 25.1) nmol/min/g tumor wet weight, respectively. Thirty-six % of the glucose and 25% of the glutamine supplied to the tumors was utilized. Comparison (by linear regression and analysis of covariance) of the rates of supply and utilization of glucose and glutamine in tumors growing in fasted versus fed rats indicated that these substrates are utilized more efficiently by tumors growing in fasted animals. Lactic acid was either produced or utilized, depending on the arterial whole-blood concentration. Production or utilization occurred, respectively, when the arterial lactate concentration was less or greater than 1 to 3 mM. The arterial whole-blood amino acids (except glutamine) were utilized at rates that ranged from 1 to 4 nmol/min/g tumor wet weight. The results indicate that energy production for tumor growth in fasted rats is supported, in part, by an increased availability of ketone bodies, by an increased efficiency of utilization of glucose and glutamine, and, under certain circumstances, by utilization of lactic acid.

3-Hydroxybutyric Acid↗
PubMed1982

Mitochondrial malic enzymes. Purification and properties of the NAD(P)-dependent malic enzyme from canine small intestinal mucosa.

An NAD(P)-dependent malic enzyme with a specific activity of 40.6 mumol of NADH/min/mg of protein and an isoelectric point of 5.4 was purified to apparent homogeneity from canine small intestinal mucosal mitochondria. The purification procedure employed ammonium sulfate fractionation, Sepharose CL 6B gel filtration, chromatography on DEAE-cellulose to remove the interfering malate dehydrogenase, and affinity chromatography on 2',5'-ADP-Sepharose and NAD-agarose to take advantage of the dual coenzyme specificity. Antibody prepared from the purified enzyme produced a single peak upon cross-rocket immunoelectrophoresis against the mitochondrial sonicate. Continuous polyacrylamide gel electrophoresis showed NAD and NADP activity co-migrating with the native protein band. A single band of protein having an apparent Mr = 62,000 was seen on sodium dodecyl sulfate electrophoresis. At pH 7.3, gel filtration revealed a single peak of activity with NAD and NADP corresponding to an apparent Mr = 282,000. Gradient gel polyacrylamide electrophoresis at pH 9.0 indicated an additional broad band of activity corresponding to a Mr = 141,000. Under physiological conditions therefore the protein appears to exist as a tetramer of Mr = 282,000 composed of four equal subunits, whereas at elevated pH values during electrophoresis, partial dissociation to a dimeric species occurs.

Animals↗
PubMed1980

Mitochondrial malic enzymes. An association between NAD(P)+-dependent malic enzyme and cell renewal in Sprague-Dawley rat tissues.

The activities of the mitochondrial NAD(P)+- and NADP+-dependent malic enzymes were measured in 11 tissues of the male Sprague-Dawley rat. The NAD(P)+-dependent malic enzyme was present in small intestinal mucosa, spleen, thymus, lung, and testis. Each of these tissues contain cells that are undergoing active rates of renewal. The NADP+-dependent malic enzyme was not confined to tissues undergoing cell renewal, and was present in mitochondria from brain, skeletal, and heart muscle, kidney, and lung and testis. Both enzymes were absent or at a low activity in normal and regenerating liver. The results support, and extent to nonneoplastic tissues, our proposal that cells which show active and sustained rates of renewal contain the NAD(P)+-dependent malic enzyme and have a unique intramitochondrial pathway for malate oxidation (Sauer, L.A., Dauchy, R.T., Nagel, W.O., and Morris, H.P. (1980) J. Biol. Chem. 255, 3844-3848).

Animals↗
PubMed1977

On the mechanism of the Crabtree effect in mouse ascites tumor cells.

The addition of glucose to ELD and ELT/B1 mouse ascites tumor cell suspensions caused a 2.3-fold increase in the phosphorylation state ratio, (ATP)/(ADP) (Pi), because of a decrease in the intracellular Pi concentration. The addition of glucose to these cell suspensions has been reported by Chance and Hess ('59) to cause an increase in the study state reduction of cytochrome b and an increase in the steady state oxidation of cytochrome c. On a quantitative basis these two independent measurements suggest that a near equilibrium exists between the oxidation-reduction state of the mitochondrial electron carriers and the reactions of ATP synthesis (as expressed by the phosphorylation state ratio) both before and after glucose addition. We conclude that the mechanism of the inhibition of respiration by glycolysis (the Crabtree effect) is a decrease in the rate of electron transport caused by the mass action effect of the elevated phosphorylation state ratio.

Adenosine Diphosphate↗
PubMed1977

Pregnenolone-binding proteins in the rat adrenal cortex.

Rat adrenal cortex contains a protein(s) that binds pregnenolone with high affinity. This binding, demonstrated by gel filtration and by a dextran-coated charcoal method, was associated with the cytosol and with fractions solubilized by sonication from the mitochondria and microsomes. The binding of pregnenolone was saturable and was inhibited by mercurials and proteolytic enzymes. Pregnenolone-binding was not influenced by the presence of progesterone, deoxycorticosterone, corticosterone or aldosterone, but was inhibited by steroids with a 3beta-hydroxy-5-ene structure similar to pregnenolone, and by hydroxymethylene steroid and cyanoketone. We suggest that this protein is involved in the intracellular transport and retention of pregnenolone within adrenal cortical cells.

Adrenal Cortex↗