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Biomedical subjects

D Kunze

Publications and source records attributed to D Kunze.

At least 55 records · Page 3Linked to original sources

Phosphatidic acid phosphatase activity in subcellular fractions of normal and dystrophic human muscle.

Biopsy samples from normal and dystrophic human muscle (Duchenne type) were fractionated by differential centrifugation and microsomes, mitochondria and cytosol were assayed for phosphatidic acid phosphatase (EC 3.1.3.4) and marker enzymes of mitochondria and cytosol. The activity of phosphatidic acid phosphatase was significantly lower in microsomes and higher in cytosol and mitochondria of dystrophic muscle than in the corresponding subcellular fractions of normal muscle. The results support an explanation of earlier findings that there is reduced G3P incorporation into diglycerides and phosphatidylcholine and a qualitative and quantitative change in the amount of phosphatidylcholine in dystrophic microsomes. The possible reasons for the reduction in the activity of only microsomal PA-P-ase were discussed.

Animals↗

[Cell membrane differences between malignant and nonmalignant cells].

Malignant cells possesses an electric surface charge differing from their healthy counterparts. In many cases they exhibit increased electronegativity. We incubated blood or bone marrow with heparin--a polyanion--and subsequently stained the cells with a fluorochrome. In healthy subjects or patients with non-malignant disease heparin was found to attach closely to the cell surface, visualised through fluorescence. In a variable number of malignant cells heparin did not attach to the cell surface. Electrostatic repulsion of the negative heparin molecule through the increased negativity of the malignant cell is discussed as an explanation of this finding which can be corrected/inhibited by neuraminidase incubation.

Blood Cells↗

[Value of histopathologic findings following liver transplantation based on biopsy course studies].

A total of forty-four biopsies from nine liver transplantation patients, who had developed complications postoperatively, were studied histologically and, in part, electron-microscopically. Morphologic signs of acute rejection were seen in three patients, while there were indications of chronic rejection in one patient. In combined lesions, such as drug-induced hepatosis, cholangitis, hepatitis, and rejections, the interpretation of biopsy findings may be difficult, and special entities cannot in every case be separated unequivocally. Changes of serum bilirubin and of serum enzyme activity do not run entirely parallel to the microscopically detectable structural lesions. For diagnosis of complications after liver transplantation both the morphologic and the clinical findings must be considered.

Adult↗

The availability of endogenous and exogenous disaturated diacylglycerol for the diacylglycerol-consuming reactions in lung microsomes.

Lung tissue is characterized by its high level of dipalmitoylphosphatidylcholine, which can be synthesized by lung microsomes with endogenous and exogenous 1,2-dipalmitoylglycerol as the substrate. This endogenous substrate species was also available for the triacylglycerol synthesis but not for the de novo synthesis of phosphatidylethanolamine. From exogenous disaturated diacylglycerol the corresponding species of phosphatidylcholine, triacylglycerol and also phosphatidylethanolamine were formed. These results support the thesis that endogenous disaturated diacylglycerol is not available for all diacylglycerol-consuming reactions.

Acyltransferases↗

Diacylglycerol species in microsomes and mitochondria of normal and dystrophic human muscle.

The concentration of 1.2-diacylglycerol in mitochondria and microsomes of normal human muscle was estimated to be 1.7 +/- 0.6 and 9.2 +/- 1.9 nmol X mg protein-1, respectively. The molecular species profile of 1.2-diacylglycerol was obtained using high pressure liquid chromatography which yielded 14 fractions. Corresponding studies were carried out for normal and dystrophic muscle. No significant difference could be seen between the 1.2-diacylglycerol patterns in normal muscle mitochondria and in microsomes. There was a radical shift in the 1.2-diacylglycerol pattern in both dystrophic organelles, mainly with a decrease in 16:0/16:0 species. In dystrophic mitochondria the total level of 1.2-diacylglycerol was higher.

Diglycerides↗

Glycerophosphate acylation by microsomes and mitochondria of normal and dystrophic human muscle.

The incorporation of [14C]glycerophosphate into phosphatidic acid, diacylglycerol, triacylglycerol and phosphatidylcholine by microsomes and mitochondria prepared from normal and dystrophic human muscle incubated in vitro in the presence of 0.3 mmol/l CDP-choline was measured. In mitochondria only phosphatidic acid and diacylglycerol are labelled; the rate of incorporation into these two compounds showed no difference between dystrophic and normal mitochondria. In dystrophic microsomes the incorporation into phosphatidic acid was delayed and decreased. No incorporation of glycerol into diacylglycerol, phosphatidylcholine and triacylglycerol could be measured. Thus in dystrophic muscle microsomes only PA was labelled during an incubation of up to 45 min. In both types of microsomes the concentration of endogenous free fatty acids and diacylglycerol was nearly identical. The level of phosphatidylcholine was 186 and 79 nmol/mg microsomal protein in normal and dystrophic muscle microsomes, respectively. Whether the results could be explained as secondary changes was discussed. Despite some unsolved problems the conclusion was drawn that a better explanation of the results is to assume a primary defect involving microsomal-bound phosphatidic acid phosphohydrolase and possibly glycerol-P-acyltransferases.

Acylation↗

Synthesis of phosphatidylcholine and phosphatidylethanolamine in relation to the concentration of membrane-bound diacylglycerols of rat lung microsomes.

Different concentrations of membrane-bound diacylglycerol were generated in vitro in rat lung microsomes by treatment with CMP. Diacylglycerol concentrations of between 16 (endogenous content) and 48 nmol/mg of microsomal protein were obtained. The relative proportion of the disaturated species of diacylglycerol remained constant at all diacylglycerol concentrations. Choline- and ethanolaminephosphotransferase activity was determined in relation to the diacylglycerol concentrations of microsomes. The activity of both phosphotransferases increased. The relative proportion of disaturated phosphatidylcholine synthesized at each diacylglycerol concentration was nearly the same and corresponded to the relative proportion of the disaturated species in the diacylglycerol. Disaturated phosphatidylethanolamine was not formed. The affinities of the choline- and ethanolaminephosphotransferases for the diacylglycerol substrate were different. We conclude that the cholinephosphotransferase is generally non-selective for the diacylglycerol substrate. The available diacylglycerol pattern seems to govern the species pattern of phosphatidylcholine and phosphatidylethanolamine. The kinetics of the phosphotransferases regulate the mass proportion of these phospholipids.

Animals↗

Dynamic discharge characteristics of low pressure receptors in the rat.

An in vitro preparation was used to examine the discharge of low pressure receptors in response to a pulsatile pressure stimulus. Both slowly adapting and rapidly adapting receptors were examined. After an increase in the mean level and/or dP/dt of a pulsatile pressure input, the discharge of slowly adapting receptors reached a steady state level within 2 minutes. An increase in mean pressure, with constant pulsatile amplitude and dP/dt, produced a sustained increase in the number of spikes/cycle, in the average number of spikes/second, and in the average frequency during the burst within the cycle. In slowly adapting receptors, an increase in dP/dt at a constant mean pressure and pulsatile amplitude produced a decrease in the number of spikes/cycle and an increase in both the average number of spikes/second and the frequency during the burst. Rapidly adapting receptors showed very different characteristics, responding to a pulsatile pressure input above threshold with an irregular discharge which averages approximately 1 spike/cycle at all mean pressure levels. Although rapidly adapting receptors transiently increased their discharge in response to an increase in mean pressure, within 60 seconds discharge returned to the pre-increase level. Rapidly adapting receptors continued to discharge with an average of 1 spike/cycle as dP/dt was increased. Since dP/dt was raised by increasing the frequency of the pulsatile input, the number of spikes/second increased. In the steady state, slowly adapting receptors transmit information reflecting mean pressure levels. They are also sensitive to the rate of change of pressure. Rapidly adapting receptors, on the other hand, are insensitive to mean pressure but do respond to the frequency of the stimulus.

Animals↗

Phospholipase A activation following extracorporeal circulation and its blockade by procaine.

The phospholipase A activity of human plasma was investigated in the course of operations with the aid of extracorporeal circulation. After an initial increase following heparin application, there is a continuous rise up to the end of perfusion and a decrease to normal values 30 minutes after the end of perfusion and the application of protamine. Procaine is suitable for the inhibition of the increased phospholipase A activity. In accordance with in vitro determinations of an effective dose of 1 mmol/ml, corresponding concentrations were attained with an infusion rate of 1.5-2 mg/kg/min. In a second series of investigations, a significantly smaller phospholipase A activation in the course of perfusion was detectable through the addition of procaine.

Coronary Artery Bypass↗

Some examples of the clinical importance of the basic and heparin-induced phospholipase A in human plasma.

Phospholipase A activity was determined in human plasma with biological 32P-labelled phosphatidylethanolamine from rat liver following cardiac operations with the aid of the heart-lung-machine. The basic activity before heparin and the initiation of bypass was 72 nmol . ml-1 . h-1 plasma; thereby large differences in the basic activity were detected between cyanotic and acyanotic heart diseases. A sharp increase of phospholipase activity was observed after heparin (a smaller one in intensive care patients with low-dose heparin), and a further increase up to the end of perfusion. Normal values are reached after giving protamine at the end of the operation. An important role for plasma phospholipase in the regulation of physiological and pathophysiological processes may be supposed from these results.

Child, Preschool↗

The antenatal use of ambroxol (bromhexine metabolite VIII) to prevent hyaline membrane disease: a controlled double-blind study.

A prospective double-blind clinical trial was carried out to determine whether ambroxol (bromhexine metabolite VIII) treatment (1000 mg/day for a period of 5 days) reduces the risk of hyaline membrane disease (HMD) in potentially premature infants. Amniocentesis was performed before the first and 24 h after the last application of ambroxol or placebo to assess the development of the total phospholipid phosphorus content, the L/S ratio, the P/S ratio, and the properties of the surface tension of the amniotic fluid after ambroxol or placebo. There were 246 infants born to 224 mothers. Of the 116 infants with less than or equal to 36 completed weeks' gestation, 56 were in the ambroxol and 60 in the placebo group. No differences between groups occurred in risk factors for HMD (diabetes, asphyxia, male sex, cesarean section). Statistically significant differences in favor of the infants in the ambroxol group were found in the HMD incidence: 23.2% in the ambroxol group compared with 41.7% in the placebo group (p less than 0.05). There was no reduction of the HMD incidence in the less than or equal to 32-week gestational age category in the ambroxol group compared with the placebo group inspite of the fact that all the examined parameters for determining lung maturity reflected a stimulatory effect of ambroxol compared with the results of the placebo group, particularly before the 33rd week of gestation. Prolonged rupture of the membranes played no protective role against HMD.

Ambroxol↗