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Biomedical subjects

P Schauder

Publications and source records attributed to P Schauder.

At least 19 recordsLinked to original sources

Comparison between transport and degradation of leucine and glutamine by peripheral human lymphocytes exposed to concanavalin A.

Transport and pathways of leucine and glutamine degradation were evaluated in resting human peripheral lymphocytes and compared with the changes induced by concanavalin A (ConA). Cells were incubated with [1-14C]leucine (0.15 mM), [U-14C]leucine (0.15 mM), or [U-14C]glutamine (0.4 mM) after culture with or without 2, 5, 7, or 10 micrograms/ml ConA for 2, 18, or 24 hours, respectively. Initial rates of transport of leucine and glutamine were augmented 2.7-fold and threefold by the mitogen. Leucine transamination, irreversible oxidation, and catabolism beyond isovaleryl-CoA were increased by 90%, 20%, and 60%, respectively. Glutamine utilization increased threefold; accumulation of glutamate, aspartate, and ammonia increased by 700%, 50%, and 100%, respectively, and 14CO2 production by about 400% in response to ConA. The results indicate that ConA stimulates to about the same extent transport of leucine and glutamine into lymphocytes. Glutamine is mainly channeled into catabolic pathways, while leucine remains largely preserved. It is suggested that these metabolic changes provide more leucine for incorporation into protein and more N- and C-atoms required for the synthesis of macromolecules and energy from glutamine.

Ammonia

Characterization of glutamine transport into resting and concanavalin A-stimulated peripheral human lymphocytes.

Characteristics of glutamine transport, its substrate specificity, and its pattern of competitive and non-competitive inhibition in response to amino acid analogues were determined in peripheral human lymphocytes, incubated with or without concanavalin A (Con A). Maximum capacity of transport (Vmax) at 37 degrees C and 136.9 mM Na+ was 30 pmol/10(6) cells/30 seconds, while the apparent Km was 142 microM. In cells exposed to 10 mM histidine, asparagine, serine, or leucine transport of glutamine declined to 28%, 15%, 17%, and 21%, respectively, of the rates in controls. Inhibition by histidine (Ki = 0.58 mM) and serine (Ki = 0.25 mM) was competitive, by leucine was non-competitive (Ki = 0.64), while alpha-methylamino-isobutyric acid and 2-amino carboxy-bicyclo (2.2.1)-heptane had no effect. In cells cultured for 24 hours with or without 10 micrograms/ml Con A, the apparent Km was 70 microM vs. 89 microM and Vmax 73 vs. 26 pmol/10(6) cells/30 seconds. Sodium depletion (9.0 mM NaCl) greatly diminished glutamine transport in resting and stimulated cells. Inhibition of glutamine transport by serine was sodium sensitive, while inhibition by histidine and asparagine was not. Serine had no competitive effect in sodium-depleted media. The data demonstrate what appear to be two carrier systems for glutamine, sodium sensitive and sodium insensitive. It is suggested that glutamine transport into lymphocytes occurs via processes similar to System N and System ASC described in other cells, with System ASC as the sodium-sensitive component. Con A augments the capacity rather than the affinity of glutamine transporting systems.

Adult

[Diagnosis and prevalence of latent hepatic encephalopathy].

To compare the efficacy of various psychometric and neurophysiological tests in the detection of latent hepatic encephalopathy (LHE) cerebral functions were studied in 146 patients with liver cirrhosis but without overt encephalopathy and in 146 matched controls. Patients with liver cirrhosis scored significantly worse than controls in 8 out of 11 tests. Best discrimination between patients with cirrhosis and controls was obtained by testing for reaction time to white and colored light with a reaction time apparatus (DTG), and with the digit symbol (UT1) and block design test (UT4), i.e. with two Wechsler adult intelligence scale performance tests. Thirtyseven out of 146 (25%) patients with cirrhosis reveiled an abnormal result with the DTG alone. A combination of the DTG, UT1 and UT4 yielded the diagnosis in 44 (30%) patients. LHE correlated with the severity of the disease (Child-Pugh classification) but not with its etiology or with portasystemic shunting. In the Federal Republic of Germany about 300,000 subjects suffer from liver cirrhosis. Based on our results 100,000 of them may have LHE.

Adult

[Home parenteral feeding in advanced tumor diseases].

Twenty selected patients with advanced malignant tumour (11 women and 9 men; mean age 52.8 [17-83] years) were on home parenteral nutrition because of ileus and (or) shortintestine syndrome. Mean survival time after onset of total parenteral nutrition in hospital was 107 (23-467) days. Mean treatment period at home was 81 (13-376) days, in hospital 26 (3-91) days. The patients with the shortest survival time all had metastasizing gastric carcinoma. The most common complaint was physical fatigue. In one patient there was a treatment-related complication (catheter sepsis). The results document that total parenteral home nutrition of carefully selected patients with advanced malignant tumour makes it possible for the remaining period of life to be spent, in acceptable conditions, at home rather than in hospital.

Adolescent

[Incorporation of 15N in VLDL and LDL: in vivo synthesis of apolipoprotein B in the post-absorptive and fasting state].

In vivo synthesis of apolipoprotein B 100 (ApoB) was recently determined in man using stable isotopes. With this procedure we analyzed (1) the effect of fasting on synthesis of ApoB from very low density lipoprotein (VLDL) and (2) tracer enrichment in low density lipoprotein (LDL). After a 36-hour fasting period and in the post-absorptive state 4 healthy subjects were given a priming dose (8.7 mumol/kg) of 15N glycine followed by a constant infusion (10 mumol/kg/h for 8 h) to achieve 5% tracer enrichment in the plasma pool of glycine. The K-values, i.e. fractional synthetic rates/hr of ApoB from VLDL were 0.53 +/- 0.26 vs. 0.43 +/- 0.16 (p greater than 0.05). Tracer enrichment in ApoB from LDL at the end of the infusions was 0.19% vs. 1.46% in ApoB from VLDL. The results indicate that (1) in young healthy postabsorptive individuals about 40% of ApoB from VLDL in plasma is synthesized per hour, (2) fasting does not materially affect fractional ApoB synthesis and (3) at 5% 15N enrichment in plasma glycine, tracer enrichment in ApoB from LDL is at the lower limit of detection for the procedure employed.

Adult

Regulation of leucine transport and oxidation in peripheral human lymphocytes by glutamine.

In this study we investigated the influence of physiological levels of glutamine, isoleucine, and valine on leucine oxidation and transport by peripheral lymphocytes in an in vitro system. The presence of glutamine in the incubation mixture inhibited leucine oxidation by 61%. This effect was not significantly augmented by addition of isoleucine and valine. Leucine transport revealed a Km of 124 mumol/L and a Vmax of 24 pmol/10(6) cells/30 sec. Glutamine inhibited leucine transport by 63%. The capacity of lymphocytes for leucine transport exceeded the capacity for leucine oxidation by a factor of 7.8 (13.6 +/- 0.6 v 1.74 +/- 0.1 pmol/10(6) cells/30 sec). It is concluded that glutamine is a regulator of leucine transport and oxidation in human peripheral lymphocytes, and the inhibition of leucine oxidation by glutamine is not due to an alteration of leucine transport but reflects an intracellular event.

Biological Transport

Assessment of effects of amino acids and branched chain keto acids on leucine oxidation in human lymphocytes.

Effects of amino acids and branched chain keto acids on leucine transamination and oxidation were assessed in peripheral human lymphocytes. Isoleucine (80-200 mumol/l) and valine (250-500 mumol/l) diminished transamination and oxidation of leucine up to 25%, glutamine (50-1000 mumol/l) up to 55%. alpha-Ketoisocaproic acid (KIC; 200 mumol/l) augmented the activity state of branched chain keto acid dehydrogenase by 40%. It is concluded that in peripheral human lymphocytes (1) isoleucine, valine and glutamine are physiological inhibitors of leucine catabolism, and (2) leucine can promote its own degradation via KIC.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)

[Ambulatory parenteral nutrition in short bowel syndrome: a retrospective study].

Parenteral nutrition via an indwelling central venous catheter was undertaken at home over a total period of 24,747 days in 34 patients with the short-bowel syndrome (of various causes). In some of the patients there developed complete adaptation of the residual intestine so that parenteral nutrition could be terminated. Complications were: infection, thrombosis, pulmonary embolism and metabolic problems. But the method proved to be suitable for improving the quality of life of these patients.

Adolescent

Sex-specific differences in plasma branched-chain keto acid levels in obesity.

Obesity was associated with a significant increase in postabsorptive plasma concentrations of the branched-chain keto acids in men but not in women matched for body-mass index and age. Plasma glucose and serum insulin were significantly higher in obese subjects than in nonobese control subjects. Obese women had more adipose tissue than did obese men from the sum of triceps and subscapular skinfold thickness. It is suggested that augmentation in plasma branched-chain keto acids in obesity may reflect insulin resistance and that the apparent differences observed between obese women and men may be due to differences in body composition.

Blood Glucose

[Significance of branched-chain keto acids for protein metabolism].

Branched chain keto acids may offer therapeutic benefits for clinical conditions associated with nitrogen accumulation or increased proteolysis. The effects of keto acids on protein metabolism are complex. Mechanisms such as (1) transamination to the respective amino acids, (2) inhibition of proteolysis, (3) stimulation of insulin secretion, and (4) augmentation in the activity of BCKA-decarboxylase need to be considered. Presently, therapy with branched chain keto acids is still experimental.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)

Effect of fasting on the release of insulin and somatostatin from perifused islets of Langerhans.

Release of somatostatin and insulin from perifused islets of fasted and control rats was compared. After a fasting period of 48 h glucose-induced insulin release but not somatostatin release was diminished. Islets from fasted rats released significantly more somatostatin in the presence of 3.3 mM glucose than islets from controls. Simultaneously, the somatostatin content of isolated islets from fasting rats was significantly decreased. The results indicate that the low secretory activity of islet B cells in the fasting state is associated with a high secretory activity of islet D cells.

Animals