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Biomedical subjects

R Scholz

Publications and source records attributed to R Scholz.

At least 55 records · Page 3Linked to original sources

Normal insulin receptor tyrosine kinase activity and glucose transporter (GLUT 4) levels in the skeletal muscle of hyperinsulinaemic hypertensive rats.

The spontaneous hypertensive rat is an animal model characterized by a syndrome of hypertension, insulin resistance and hyperinsulinaemia. To elucidate whether in analogy to other insulin resistant animal models an inactivity of the insulin receptor kinase or an alteration of the glucose transporter (GLUT 4) level in the skeletal muscle might contribute to the pathogenesis of insulin resistance we determined insulin receptor kinase activity and GLUT 4 level in the hindlimbs of spontaneous hypertensive rats and normotensive control rats. Normotensive normoinsulinaemic Lewis and Wistar rats were used as insulin sensitive controls, obese Zucker rats were used as an insulin resistant control with known reduced skeletal muscle insulin receptor kinase activity. Binding of 125I-insulin, crosslinking of 125I-B26-insulin, autophosphorylation in vitro with 32P-ATP and phosphorylation of the synthetic substrate Poly (Glu 4: Tyr 1) were performed after partial purification of solubilized receptors on wheat germ agglutinin columns. GLUT 4 levels were determined by Western blotting of subcellular muscle membranes. Insulin receptors from spontaneous hypertensive rats compared to those from Lewis and Wistar rats showed no difference of the binding characteristics or the in vitro auto- and substrate phosphorylation activity of the receptor, while in the Zucker rats the earlier described insulin receptor kinase defect was clearly evident. Western blots of subcellular muscle membrane fractions with antibodies against GLUT 4 revealed no difference in transporter levels. These data suggest that insulin resistance in spontaneous hypertensive rats is caused neither by an insulin receptor inactivity nor by a decreased number of glucose transporters in the skeletal muscle.

Adenosine Triphosphate↗

Soluble CD8, CD25 and CD30 antigens as prognostic markers in patients with untreated Hodgkin's lymphoma.

In a search for serum markers with prognostic value and specificity for disease activity in Hodgkin's lymphoma, we evaluated the clinical significance of soluble suppressor/cytotoxic T-cell antigen (sCD8), soluble interleukin-2 receptor (sCD25) and soluble Hodgkin's associated antigen (sCD30) levels in the serum of 90 patients with untreated Hodgkin's lymphoma (HD). HD patients in advanced stages had significantly higher sCD8 and sCD25 levels than normal controls. The rate of detectable sCD30, which was absent in healthy controls, depended on stage and histological subtype, and was 22% for the entire group. Low sCD25 levels (< 1000 U/ml) predicted an excellent prognosis (100% event-free survival), while patients with high sCD8 levels (> 750 U/ml) or the demonstration of sCD30 had a poor outcome. Therefore, all three markers have prognostic significance. However, only sCD30 correlated strictly with disease activity and seems to be of value for the follow-up of patients in remission.

Adolescent↗

Olsalazine-related diarrhoea: does rat intestine adapt in vivo?

Diarrhoea may occur in up to 10% of patients with ulcerative colitis treated with olsalazine, the azolinked dimer of 5-aminosalicylic acid. However, this symptom often disappears despite continued drug medication. To examine reversibility of and adaptation to olsalazine effects on intestinal absorption, rats were fed olsalazine (4 mg/100 g body weight/day) for 0 (controls), 12, 24, and 32 days. Jejunal, ileal, and colonic loops were perfused in situ with buffer or olsalazine (11.6 mM) in a pendular perfusion system. Water and electrolyte absorption was inhibited in all intestinal segments (p less than 0.001). In the proximal small intestine, however, sodium absorption was inhibited by 61%, whereas chloride and potassium absorptions were turned into net secretion. In contrast, in ileal and colonic segments sodium, chloride, and potassium absorptions were turned into a net secretion. All inhibitory effects were reversible within a short time. Intestinal absorption remained inhibitable compared with controls (p = not significant) after chronic administration of olsalazine even for 1 month. Jejunal monosaccharide absorption was not altered by acute olsalazine perfusion. In the ileum, glucose absorption was significantly inhibited, but the inhibitory capacity of acute olsalazine application decreased significantly (p less than 0.05) depending on duration of olsalazine pretreatment (51% (controls) versus 38% (32 days)). These results point to a complex, acute, but fully reversible effect of olsalazine on intestinal passive and chloride-coupled absorptive processes. Since a mucosal adaptation to these diarrheogenic effects does not occur, the resulting increase in fluid load on the diseased colon may be important in the pathogenesis of olsalazine-related diarrhoea.

Adaptation, Physiological↗

The clinical significance of cytokines and soluble forms of membrane-derived activation antigens in the serum of patients with Hodgkin's disease.

In a search for specific serum markers with prognostic impact in Hodgkin's Disease (HD), we evaluated the clinical significance of several cytokines (IL-1 beta, IL-2, IL-3, IL-6, G-CSF, GM-CSF, TNF-alpha) and soluble forms of membrane-derived antigens (sCD4, sCD8, sCD23, sCD25, sCD30) in the serum of patients with untreated HD. Elevations of three groups of serum factors were observed: Firstly, elevations of the hematopoietic cytokines GM-CSF (detected in 39%), IL-6 (57%) and IL-3 (13%), which occurred simultaneously in the majority of the cases; secondly, simultaneous elevations of the inflammatory cytokines TNF-alpha and IL-1 beta (detected in 7%); and finally, elevations of membrane-derived activation antigens sCD8, sCD25, and sCD30. While the cytokine levels did not correlate with other obvious parameters, the membrane-derived activation antigens sCD8, sCD25 and sCD30 were associated with a poor prognosis. Only sCD30 correlated with disease activity and holds promise for the follow-up of patients in remission. Further investigations of these parameters at the cellular level might help to elucidate the enigmatic biology of HD.

Antigens, CD↗

Increased levels of circulating cytokines in patients with untreated Hodgkin's disease.

Expression of several cytokines has been demonstrated in Hodgkin and Reed-Sternberg (H&RS) cells in vitro and in vivo. In order to determine whether interleukin-1 beta (IL-1 beta), IL-3, IL-6, GM-CSF, G-CSF, and TNF-alpha are elevated in Hodgkin's disease (HD), we tested the sera of untreated patients with HD by means of sensitive sandwich ELISAs. GM-CSF was detected in 22/56 patients (39%; range 40-140 pg/ml), IL-3 in 5/40 (13%; range 13-26 pg/ml), and IL-6 in 32/56 patients (57%; range 12-332 pg/ml). TNF-alpha and IL-1 beta were detected in only 3/43 patients (7%; range: TNF-alpha: 36-66 pg/ml; IL-1 beta: 389-1505 pg/ml) and G-CSF not at all. All patients with measurable IL-3 levels had both elevated IL-6 and GM-CSF levels, and the majority of patients with elevated IL-6 also had elevated GM-CSF levels and vice versa. In contrast, the 3/40 patients with both measurable IL-beta and TNF-alpha did not have elevated IL-3, IL-6, or GM-CSF levels. Cytokine levels were independent of stage or the presence of B-symptoms, and there was no correlation with any other clinical or laboratory parameter. Elevations of the respective cytokines might be a means to maintain normal blood cell counts in the respective patients with HD.

Adolescent↗

[Mass screening of blue color vision in divers with the desaturated Lanthony-15-Hue Test].

We tested 1002 persons, 572 divers (including 38 who had diving accidents) and 430 nondivers, for defects of the blue-sensitive system during the years 1988 and 1989. Recent research has shown functional disorders of color vision in divers, linked to previously described alterations of the retinal capillary system and pigment epithelium. The desaturated Lanthony-15-HUE test was used as a screening method. No defect of the blue-sensitive system was found, either in divers or in nondivers. Our results are similar to those of other researchers. One exception was that we found no correlation between age and error score. We found no evidence for retinal damage caused by diving.

Adult↗

[Intra- and extra-capsular condyle fractures in the growth period. Therapy, clinical course, complications].

37 patients had been reviewed after surgical (n = 25) or conservative (n = 12) treatment of condylar fractures. Morphologic and functional outcomes were equal in spite of the poorer starting position of the patients that had been operated on. Injuries and complications due to the operation, such as facial nerve palsy, growth inhibition or obvious scars have never been found. Conservatively treated and operated patients alike showed a moderate limitation of opening and mediotrusion on the fracture side, and both groups showed a flattening of the protrusion path.

Adolescent↗

[Midfacial and mandibular fractures during the growth period].

This study investigated the occurrence of primary and secondary complications following conservative versus surgical intervention in the treatment of midface and lower jaw fractures. Follow-up studies were undertaken on 81 patients who had been admitted to the above clinic with such fractures during their adolescence. It was found that more complications developed after surgical intervention.

Adolescent↗

Influence of disposable ('Conchapak') and reusable humidifying systems on the incidence of ventilation pneumonia.

The contamination of disposable ('Conchapak') and reusable humidifying systems and their influence on the incidence of pneumonia was studied in 116 patients requiring continuous mechanical ventilation therapy. The water reservoirs of 11 (15.9%) of the 69 disposable systems became colonized, but all reusable systems were found to be sterile. In four of the 11 samples, the organisms isolated corresponded with those cultured from tracheal secretions several days before. Ventilator-associated pneumonia occurred in 36 (31.0%) of the patients, but there was no statistically significant difference in the incidence of pneumonia between the patients treated with the disposable or the reusable humidifying systems. Gram-negative bacteria were the predominant organisms isolated from tracheal aspirates of patients who developed ventilator-associated pneumonia. These results suggest that disposable humidifying systems do not influence the rate of ventilator-associated pneumonia in mechanically ventilated patients.

Adult↗

Control of energy metabolism by glucagon and adrenaline in perfused rat liver.

Changes in subcellular distribution of adenine nucleotides, mitochondrial/cytosolic proton gradients, rates of respiration, gluconeogenesis (fasted state) and glycogenolysis (fed state) were studied in isolated perfused rat livers following addition of glucagon (10(-8) M) or adrenaline (10(-7) M). Glucagon increased the gradient in all states. The cytosolic ATP/ADP ratio was increased in the fasted but decreased in the fed state which is consistent with a diminished futile cycling in gluconeogenesis (fasted state) or a decreased glycolytic rate (fed state). Adrenaline caused an increase in the proton gradient and the mitochondrial ATP/ADP ratio. The two effects are attributed to increased calcium entry into the matrix space.

Adenosine Diphosphate↗

Does the pentose cycle play a major role for NADPH supply in the heart?

It was attempted to determine the substrate flux through the pentose cycle in isolated rat hearts which performed pressure-volume work employing 14CO2 production from [1-14C]glucose (Kühn & Scholz (1982) Eur. J. Biochem. 124, 611-617). Even under conditions of increased NADPH requirements (infusion of tert-butylhydroperoxide) and a diminished 14CO2 production from glucose via the citrate cycle (in the presence of oleate as additional substrate) or enhanced activity of glucose-6-phosphate dehydrogenase (pretreatment with isoproterenol), a substrate flux through the pentose cycle was not detectable. The lower limit of detection is 0.01 mumol/(min X g). The increase in 14CO2 production from [1-14C]- and [6-14C]glucose and the acceleration in the washout when tert-butylhydroperoxide was present suggest an increase of substrate flux through the citrate cycle; therefore it is concluded that NADPH required for the removal of peroxides via the glutathione system is derived from the isocitrate dehydrogenase reaction.

Animals↗

Rates of pentose cycle flux in perfused rat liver. Evaluation of the role of reducing equivalents from the pentose cycle for mixed-function oxidation.

Rates of NADPH production via the pentose phosphate cycle were determined in perfused livers from phenobarbital-treated rats by measuring 14CO2 production from [1-14C]glucose infused in the presence and absence of p-nitroanisole (0.2 mM), a substrate for mixed-function oxidation. In the fed state, basal rates of NADPH generation were 34-44 mumol/g/hr. p-Nitroanisole, which was metabolized at rates of 8.9 mumol/g/hr, stimulated pentose cycle-dependent NADPH production by 21-24 mumol/g/hr. Fasting for 24 hr prior to perfusion diminished pentose cycle flux by 80% and largely abolished the stimulation of the pentose cycle by p-nitroanisole. In contrast, rates of p-nitroanisole O-demethylation were only diminished slightly, to 5.7 mumol/g/hr. Fasting decreased hepatic glucose, glucose 6-phosphate, and 6-phosphogluconate contents drastically as expected. Pretreatment of rats with 6-aminonicotinamide, which is metabolized to a potent inhibitor of 6-phosphogluconate dehydrogenase, decreased rates of NADPH generation via the pentose cycle to 6.9 mumol/g/hr but did not alter rates of p-nitroanisole metabolism (8.8 mumol/g/hr). Basal rates of NADPH generation decreased from 38 to 26 mumol/g/hr during infusion of potassium cyanide (2 mM), an inhibitor of mitochondrial energy metabolism. Cyanide also decreased rates of p-nitroanisole O-demethylation by over 60%; however, stimulation of NADPH generation via the pentose cycle by p-nitroanisole was as great in the presence (17-21 mumol/g/hr) as in the absence of cyanide. Since rates of mixed-function oxidation were unaffected after virtually complete inhibition of the pentose cycle with 6-amino-nicotinamide, it is concluded that reducing equivalents for the mixed-function oxidation of p-nitroanisole are not provided by the pentose cycle under these conditions.

6-Aminonicotinamide↗

Effect of long-chain fatty acyl-CoA on mitochondrial and cytosolic ATP/ADP ratios in the intact liver cell.

The effect of long-chain acyl-CoA on subcellular adenine nucleotide systems was studied in the intact liver cell. Long-chain acyl-CoA content was varied by varying the nutritional state (fed and starved states) or by addition of oleate. Starvation led to an increase in the mitochondrial and a decrease in the cytosolic ATP/ADP ratio in liver both in vivo and in the isolated perfused organ as compared with the fed state. The changes were reversed on re-feeding glucose in liver in vivo or on infusion of substrates (glucose, glycerol) in the perfused liver, respectively. Similar changes in mitochondrial and cytosolic ATP/ADP ratios occurred on addition of oleate, but, importantly, not with a short-chain fatty acid such as octanoate. It is concluded that long-chain acyl-CoA exerts an inhibitory effect on mitochondrial adenine nucleotide translocation in the intact cell, as was previously postulated in the literature from data obtained with isolated mitochondria. The physiological relevance with respect to pyruvate metabolism, i.e. regulation of pyruvate carboxylase and pyruvate dehydrogenase by the mitochondrial ATP/ADP ratio, is discussed.

Acyl Coenzyme A↗