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Biomedical subjects

W Bieger

Publications and source records attributed to W Bieger.

At least 19 recordsLinked to original sources

[Pseudohypertriglyceridemia in glycerokinase deficiency].

Falsely high serum triglyceride concentrations (410-850 mg/dl) were measured in four members of a family of five from Franconia in Germany. The cause was hyperglyceridaemia on the basis of glycerol kinase deficiency. None had any symptoms and no other metabolic anomaly was demonstrated. The possibility of glycerol kinase deficiency should be considered in any case of elevated serum triglyceride concentration but with clear serum, normal lipid electrophoresis and lack of response to lipid-lowering measures.

Adult

Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms.

The effects of adenosine deaminase and of pertussis toxin on hormonal regulation of lipolysis were investigated in isolated human fat cells. Adenosine deaminase (1.6 micrograms/ml) caused a two-to threefold increase in cyclic AMP, which was associated with an increase in glycerol release averaging 150-200% above basal levels. Clonidine, N6-phenylisopropyladenosine, prostaglandin E2, and insulin caused a dose-dependent inhibition of glycerol release in the presence of adenosine deaminase. Pretreatment of adipocytes with pertussis toxin (5 micrograms/ml) for 180 min resulted in a five- to sevenfold increase in cyclic AMP. Glycerol release was almost maximal and isoproterenol caused either no further increase or only a marginal additional increase of lipolysis after pretreatment with pertussis toxin, whereas cyclic AMP levels were 500 times higher than in controls. The effects of antilipolytic agents known to affect lipolysis by inhibition of adenylate cyclase activity, i.e., clonidine, N6-phenylisopropyladenosine, and prostaglandin E2, were impaired. In contrast, the antilipolytic action of insulin was preserved in adipocytes pretreated with pertussis toxin. As in controls, the peptide hormone had no detectable effect on cyclic AMP after pertussis toxin treatment. The findings support the view that the antilipolytic effect of insulin does not require adenylate cyclase or phosphodiesterase action. In addition, the results demonstrate that, upon relief of endogenous inhibition, human fat cell lipolysis proceeds at considerable (adenosine deaminase) or almost maximal (pertussis toxin) rates. A certain degree of inhibition, therefore, appears to be necessary for human fat cell lipolysis to be susceptible for hormonal activation.

Adenosine Deaminase

[Dissociation of serum kinetics of amylase and trypsin following stimulation with secretin and pancreozymin].

The diagnostic value of basal serum trypsin and amylase values in the assessment of pancreatic exocrine function is limited. Secretin injection evokes a significantly different response in the serum kinetics of trypsin and amylase, due probably to their difference in molecular weight (21,000 vs 52,000 Daltons). Serum trypsin increases in 70% of people with normal secretin-pancreozymin test after stimulation with secretin, whereas amylase remains unchanged. The post-stimulatory rise in trypsin is lower in mild exocrine insufficiency and almost completely abolished in severe exocrine insufficiency. The diagnosis of severe exocrine insufficiency is confirmed in 93% and that of mild insufficiency in 54% by low basal and post-stimulatory levels of serum trypsin. In diabetics with low basal values the post-stimulatory rise in serum trypsin confirmed normal pancreatic function. The poststimulatory kinetics of serum amylase shows no clear correlation to pancreatic function. From the divergent serum kinetics of trypsin and amylase it may be concluded that trypsin is primarily of ductular and amylase primarily of acinar origin.

Adult

[Diagnostic significance of pancreatic serum-enzyme patterns after stimulation with secretin in chronic pancreatitis (author's transl)].

The pancreatic serum evocation test with secretin has regained importance now that it is possible to determine immunoreactive trypsin and pancreatic isoamylase. After secretin stimulation there was a significant abnormal increase in serum trypsin (p less than 0.01) in 34 patients with proven chronic pancreatitis associated with mild to moderate dysfunction (groups I-II), no rise if there was marked insufficiency (group III). Patients with steatorrhoea and obstruction in the region of the head of the pancreas formed a special group because, contrary to other patients in groups III, they had marked serum enzyme rise after secretin. In 24 control subjects with a normal pancreas there was no significant change in basal pancreatic serum enzyme levels with secretin stimulation. Trypsin and amylase reaction patterns differed during secretin stimulation, with a rise in the amylase occurring at the expense of pancreas isoamylase.

Adult

Characterization of human exocrine pancreatic proteins by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis.

Exocrine proteins contained in human pancreatic juice were separated in two dimensions using isoelectric focusing and sodium dodecyl sulfate gel electrophoresis. Nineteen discrete proteins were found. Fifteen of these were identified by actual or potential enzyme activity and include three forms of trypsinogen, two forms each of procarboxypeptidase A, procarboxypeptidase B, proelastase, and colipase, and one form each for amylase, lipase, chymotrypsinogen, and prophospholipase A2. Lipase and four unidentified proteins were found to contain carbohydrate by the periodic acid Schiff staining method. Each pancreatic protein was characterized by isoelectric point and molecular weight. Proteins were quantitated according to relative mass, as measured by the incorporation of a mixture of 15 3H-amino acids into secretory proteins contained in tissue slices, and according to the distribution of Coomassie blue R stain among proteins contained in pancreatic juice, as determined by two-dimensional gel scanning and computer analysis. The second form of pancreatic procarboxypeptidase B (IEPn6.7) was present in only 4 of 10 subjects tested. Trypsinogens 1 and 3 were covalently labeled with 35SO4. Trypsin derived from trypsinogen 2 showed no inhibition with soybean trypsin inhibitor or Trasylol.

Carboxypeptidase B

Transport and utilization of amino acids and glucose in human monocytes: activation of glucose metabolism by insulin.

The influence of insulin on transport and utilization of amino acids and glucose in purified human peripheral blood monocytes has been studied. Insulin had an immediate stimulating effect on the uptake of 3-O-methylglucose and 2-deoxyglucose; the maximal effects were 55% and 47% increases, respectively, during the first 2 min, in which energy-dependent hexose uptake dominates. Later, with advancing free diffusion, values declined to 16% and 25%. After a lag of 30 min, the rise in glucose uptake was followed by a small rise in glucose oxidation, documented by an 18% increase of 14CO2 production from [1-14C]glucose in the presence of hormone. No effect of insulin on sodium dependent alpha-aminoisobutyric acid or sodium-independent leucine uptake in monocytes could be found. The incorporation of amino acids into monocyte protein remained unchanged as well. Our results prove that the well documented binding of insulin to human monocytes initiates specific cellular reactions. The increased hexose monophosphate shunt activity may result in increased immune reactivity of the monocyte.

Adult

Inhibition of K+-sensitive p-nitrophenylphosphatase activity on Rhesus-positive red cells after incubation with IgG-anti-Rhesus-D.

The incubation of ghosts derived from human Rhesus-positive red cells with IgG-anti-Rhesus-D inhibited the K+-sensitive p-nitrophenylphosphatase activity. This enzyme has a partial function in the (Na+ + K+)-ATPase system related to the phosphorylation step, which is important for active potassium transport through the red cell membrane. The specificity of the impairment by the antigen-antibody reaction in the Rhesus-D system was proved by the following controls. Ghosts obtained from Rhesus-negative red cells incubated by IgG-anti-Rhesus-D and those of Rhesus-positive red cells treated with non-immune serum did not show any reduction of the K+-p-nitrophenylphosphatase activity. The ghost preparation with lanthanum carried out after hypotonic hemolysis of the washed red cells in 2 mM LaCl3 at pH 6 was the most suitable procedure to explore this topic in comparison to other techniques for preparing ghosts of red cells.

4-Nitrophenylphosphatase

Amino acid transport in the exocrine pancreas. IV. Do glucagon or insulin mediate the in vivo effect of caerulein on amino acid transport and incorporation?

The direct in vitro effect of caerulein on pancreatic protein synthesis and amino acid transport has been investigated. In contrast to in vivo conditions we were unable to demonstrate any effect on alpha-aminoisobutyric acid and leucine uptake and on leucine incorporation usin rat pancreatic lobules. Insulin and glucagon were therefore examined as possible mediators for the in vivo effect of caerulein. Insulin (1--5 microM) slightly enhanced AIB uptake (16% but did not change uptake and incorporation of leucine. Glucagon (0.01--1 microM) was ineffective. Both islet hormones had no influence on the formation of cyclic GMP induced by secretagogue either in rat (40% increase) or in guinea pig lobules (500% increase). It seems unlikely that the two islet hormones exert any direct effect on the exocrine pancreas and thus could serve as mediators for the in vivo synthetic effect of caerulein.

Aminoisobutyric Acids

[Comparative studies on pulsatile and continuous flow during extracorporeal circulation. Effects on liver function and endocrine pancreas secretion].

The effects of pulsatile and nonpulsatile flow pattern on pancreas and liver blood flow were studied in nine dogs on cardiopulmonary bypass (CPB). Furthermore, plasma levels of glucose, insulin, glucagon, growth hormone, and cholinesterase were compared in 20 patients subjected to open heart surgery with either pulsatile or nonpulsatile perfusion. Impairment of liver and pancreas function was significantly greater at the end of CPB and 48 h afterwards with nonpulsatile flow as compared with the pulsatile flow pattern. A decrease of intestinal blood flow that was demonstrated in dogs subjected to nonpulsatile perfusion could at least in part be responsible for the difference in postoperative organ function observed in patients after CPB.

Animals

Amino acid transport in the rat exocrine pancreas. III. Effect of maximal and supramaximal hormonal stimulation in vivo.

Amino acid transport and incorporation have been studied in vitro in rat pancreatic lobules after maximal and supramaximal hormonal stimulation with caerulein. Incorporation into proteins was increased already after 30 and 120 min of maximal stimulation, but was decreased after the infusion of a supramaximal dose. Uptake of neutral amino acids was monitored using labeled leucine and alpha-aminoisobutyric acid (AIB). In the case of leucine the free pool was consistently reduced after maximal stimulation, while supramaximal doses led to an increase which could be potentiated by the addition of 2mM tetracaine. Using AIB, a significant increase in the intracellular pool was observed after maximal stimulation, conversely a decrease after supramaximal stimulation. Release of labeled leucine and AIB from preloaded lobules during incubation in the cold was significantly reduced after maximal secretory stimulation, but was found enhanced by 200 to 300 percent after supramaximal stimulation. No fine structural alterations at junctional complexes or at both the lateral and luminal plasma membranes were observed after maximal stimulation except an increased number of exocytotic figures at the luminal face. However, supramaximal stimulation led to progressive rarefaction of the tight junctional network and disintegration of the gap junctions. Concomitantly, an equal distribution of membrane particles on both faces of the plasma membrane together with a random occurrence of exocytotic figures were observed.

Amino Acids

Amino acid transport in the rat exocrine pancreas. I. Transport of neutral amino acids and their utilization in protein synthesis.

The transport and utilization of three neutral amino acids in protein synthesis was studied using isolated pancreatic lobules in vitro. The significance of the extracellular and intracellular amino acid pool in this process was analyzed removing the extracellular pool (labeled by inulin) by a cold-wash procedure. This was especially useful in short-term experiments. Double-labeling experiments indicated a predominant utilization of the intracellular amino acid pool during protein synthesis. The advantage of isolated pancreatic lobule preparations compared to tissue fragments or slices was emphasized by fine structural studies. Using freeze-etching techniques on the same preparations, differences in the distribution of membrane particles between luminal and lateral plasma membranes described earlier were confirmed, as well as the abundant occurrence of gap junctions on both membrane faces.

Amino Acids

Amino acid transport in the rat exocrine pancreas. II. Inhibition by lanthanum and tetracaine.

The two calcium antagonistic agents lanthanum and tetracaine cause severe disturbances in the secretory process of the exocrine pancreas, including inhibition of the rate of protein synthesis and exocytosis. The former effect resulted mainly from the inhibition of amino acid transport. Lanthanum in a concentration up to 1 mM inhibited transport of different species of amino acids in an unspecific way whereas tetracaine interfered specifically with the Na+ -dependent transport system for neutral amino acids (14C-alpha-amino-isobutyric acid). Na+ -dependent transport of neutral amino acids (3H-leucine) was not affected. Transport inhibition was correlated to the acitvity of the Na+, K+ -ATPase system which was measured in isolated plasma membrane fractions. At higher concentrations (5-10 mM) some uptake of lanthanum into the cells by limited endocytosis was observed. At lower concentrations lanthanum seemed to bind exclusively to certain components of the plasms membrane, mainly at the lateral and basal cell surface. Even at a concentration of 5-10 mM no binding to the apical surface occurred. Similarly no binding of lanthanum was observed to the limiting membrane of isolated zymogen granules, while mitochondria, contained in the same fraction showed considerable binding affinity. The action of lanthanum and tetracaine on membrane carrier systems did not affect the interior organization of the plasma membrane. Particle density and distribution in freeze-fracture replicas as well as the submembrane microfilamentous=microtubular system and the junctional elements remained unaffected.

Adenosine Triphosphatases