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Biomedical subjects

D Kunze

Publications and source records attributed to D Kunze.

At least 19 recordsLinked to original sources
PubMed1994

Synthesis and secretion of plasmalogens by type-II pneumocytes.

Alveolar surfactant (exposed to air and therefore a prime target of air oxidants) is supplied with antioxidants during its intracellular formation on type-II pneumocytes [Rüstow, Haupt, Stevens and Kunze (1993) Am. J. Physiol. 265, L133-L139]. Plasmalogens can protect animal cells against lipid peroxidation caused by u.v. radiation. It has been suggested that plasmalogens play a direct role in protecting animal cell membranes against oxidative stress [Zoeller, Morand and Raetz (1988) J. Biol. Chem. 263, 11590-11596]. We investigated biosynthesis and secretion of plasmalogens and phospholipids by type-II cells of adult rat lungs. The plasmalogens of type-II cells consist of 93% ethanolamine plasmalogens (EthPlas) and 7% choline plasmalogens (ChoPlas). Plasmalogens isolated from alveolar surfactant, however, consist of 36.5% ChoPlas and 63.5% EthPlas. The different incorporation rates of [14C]hexadecanol into both types of plasmalogen by type-II pneumocytes are reflected in the relative proportions of their total cellular plasmalogen content. Type-II cells cultured in the presence of labelled hexadecanol or labelled hexadecylglycerol and of labelled palmitate secrete labelled ChoPlas and labelled phospholipids, both spontaneously and in response to isoprenaline. The spontaneous and stimulated secretion rates of labelled ChoPlas are 3-6 times higher than those of labelled EthPlas. This higher relative secretion rate of ChoPlas corresponds to its higher proportion in the total plasmalogen content of alveolar surfactant compared with type-II cells. Added extracellular surfactant-specific protein A inhibits the secretion of plasmalogens as well as that of phospholipids by type-II cells. The molecular species of EthPlas and ChoPlas isolated from type-II cells or lung lavage do not differ significantly and consist mainly of molecular species containing poly-unsaturated fatty acids. We conclude that ChoPlas are secreted partly as integral constituents of the alveolar surfactant. Type-II cells select between both types of plasmalogens for secretion as a constituent of surfactant. The intramolecular sorting signal presumably is the choline moiety.

Animals↗
PubMed1994

Turner syndrome: final height, glucose tolerance, bone density and psychosocial status in 25 adult patients.

The information available on the medical and psychosocial status of patients with Turner syndrome beyond the paediatric age group is scarce. We therefore studied 25 unselected women with cytogenetically proven Turner syndrome (age 20-50 years), who never received any growth-promoting therapy, and ten control women (25-48 years). In addition to anthropometric measurements, an oral glucose tolerance test was performed, auto-antibodies to endocrine tissues were studied, bone mineral density of the forearm was measured by single photon densitometry, and information about the psychosocial distress of the patients was obtained. Adult height averaged 148.7 +/- 1.1 cm (mean +/- SE), which was 16 cm below the mean of adult women from a similar background. In Turner patients, final height correlated significantly with mid-parental height (final height = 0.67 x MPH + 32.1; r = 0.69). Body mass index was increased in Turner patients (25.6 +/- 1.3 kg/m2) compared to controls (21.4 +/- 0.6; P < 0.006). Six patients (25%) had impaired glucose tolerance or overt diabetes mellitus (one patient). Insulin release was augmented but delayed in the Turner group, and the area under the insulin stimulation curve was correlated to body mass index (r = +0.54, P < 0.01). Thyroid antibodies were detected in nine patients (37.5%). On average, bone density of the forearm was only marginally reduced compared to the age-dependent normal range. All women were employed, while only one of the Turner women was married. As a group, the subjects expressed greater distress due to infertility compared to short stature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Type II pneumocytes secrete vitamin E together with surfactant lipids.

Lung surfactant is exposed to strongly oxidizing conditions. We examined the hypothesis that in lung, lipophilic antioxidants are secreted together with surfactant to counteract the peroxidation of surfactant constituents. Lung lavage and the subfractions of the alveolar surfactant contain the lipophilic antioxidants vitamin E, vitamin A, and plasmalogens. The specific radioactivity of vitamin E isolated from serum, lung homogenate, lamellar bodies, and lung lavage increased linearly up to 3 h after intraperitoneal application of [3H]tocopherol. [3H]tocopherol was secreted in situ together with [14C]palmitic acid-labeled phospholipid in response to isoproterenol. Type II cells cultured in presence of [3H]tocopherol or of [3H]cholecalciferol and [14C]palmitic acid responded to isoproterenol by a time-dependent increase in secretion of [3H]tocopherol and of 14C-labeled phospholipids but not of [3H]cholecalciferol. The isoproterenol-stimulated secretion of [3H]tocopherol and of 14C-labeled phospholipids by type II cells is inhibited by surfactant protein A. We conclude that the alveolar surfactant contains lipophilic antioxidants as integral constituents. [3H]tocopherol seems to be secreted together with surfactant.

Animals↗
PubMed1993

The somatotropin-somatomedin axis in adult patients with Turner syndrome: measurement of stimulated GH, GH-BP, IGF-I, IGF-II and IGFBP-3 in 25 patients.

So far, few studies have addressed the regulation of GH and GH-dependent growth factors in adult patients with Turner syndrome. We therefore studied a group of 25 genetically proven patients with Turner syndrome (age 20-50 years) and 10 control women (25-48 years). Turner patients were significantly shorter (148.7 +/- 1.1 cm vs. 169.1 +/- 2.3 cm; mean +/- SE; p < 0.0001) and more overweight [body mass index (BMI)] 25.6 +/- 1.3 vs. 21.4 +/- 0.6 in controls; p < 0.01). No significant differences were present when the integrated GH response to stimulation with arginine and the serum levels of GH-binding protein (GH-BP), IGF-I, IGF-II and binding protein 3 for IGFs (IGFBP-3) were compared between the two groups. However, more detailed analysis revealed significant abnormalities of the somatotropic axis in Turner patients. Pituitary GH secretion was negatively and serum GH-BP positively related to the degree of overweight in normal patients. In Turner patients, no such relationship was present, while IGF-II significantly increased with BMI. IGFBP-3 was positively related to adult height in normal women but not in Turner patients. While serum testosterone values did not affect any of the somatotropic parameters measured, there was a previously unreported, inverse relation between serum estradiol and GH-BP in controls but not in Turner patients. While adult patients with Turner syndrome do not display endocrine features of GH insufficiency, a detailed analysis reveals several abnormalities of the interrelation between anthropometric parameters, sex steroids and the pituitary-somatomedin axis.

Adult↗
PubMed1993

Pathobiochemical aspects of cytoskeleton components.

This review summarizes pathobiochemical aspects of diseases, in which cytoskeletal components play a crucial role in pathogenesis. An attempt to classify the disorders on the basis of phenotypic changes that occur in microfilaments, intermediate filaments and microtubuli was unsuccessful. Three groups of disorders are presented: 1. cytoplasmic inclusions in specific diseases (merely descriptive); 2. diseases with genetic defects in cytoskeletal proteins (a chain of causality from defect to phenotype, in some cases with large gaps); 3. diseases with suspected involvement of cytoskeleton (hypothetical causal chain). Microfilaments are involved in certain pathogenetic processes on account of defects in their associated proteins; in Duchenne muscular dystrophy, dystrophin is defective, while the defective protein in Rett syndrome is synapsin. Defects in spectrin and membrane anchor proteins lead to disorders of the red cell membrane skeleton (congenital haemolytic anaemias). Intermediate filaments accumulate in some types of cytoplasmic inclusions, together with ubiquitin (Mallory bodies, desmin accumulation in some myopathies and others). A pathogenetic interpretation of this phenomenon is lacking. A genetic defect in certain types of keratin is the cause of epidermolysis bullosa. Interesting preliminary results are reviewed that reveal the crucial role of cytoskeletal components in a further group of diseases (intrahepatic cholestasis, Alzheimer disease, pemphigus). These disorders are currently under investigation, or are of theoretical interest with respect to the cytoskeleton. Specific reactions of cytoskeletal components in serum, which might be used diagnostically, have not been found.

Alzheimer Disease↗
PubMed1992

Studies on the formation of dipalmitoyl species of phosphatidylcholine and phosphatidylethanolamine in pulmonary type II cells.

Endogenous content of and incorporation of labelled glycerol into alkenylacyl-, alkylacyl- and diacyl-glycerol, -glycerol-3-phosphocholine and -glycero-3-phosphoethanolamine of pulmonary type II cells were measured. On prolonged incubation of type II cells with labelled glycerol, the proportion of label incorporated into the diacyl subclass of these glycerolipids increased and the proportion of label incorporated into the ether lipids declined. Endogenous phosphatidylcholine (PtdCho) of type II cells contained 38.4% of the dipalmitoyl species, but endogenous phosphatidylethanolamine (PtdEtn) only 2.5%. In contrast, similar proportions of labelled glycerol were incorporated into dipalmitoyl-PtdCho and -PtdEtn after short-time incubation but, with prolonged incubation time the proportion of labelled dipalmitoyl-PtdCho increased from 11.3 to 18.8%, whereas that of dipalmitoyl-PtdEtn did not change significantly. Type II cell membranes were found to exhibit cofactor-independent and CoA-mediated transacylations of [1-14C]palmitoyl-lyso-PtdCho and -lyso-PtdEtn. The distribution of label among the palmitic acid-containing species of PtdCho and PtdEtn formed by both transacylation activities was determined. Cofactor-independent and CoA-mediated transacylation showed a strong selectivity for palmitate and arachidonate and a strong discrimination against oleate. The amount (nmol) of dipalmitoyl-PtdEtn formed by both transacylation activities after short-time incubation (2 min) decreased with prolonged incubation time (60 min). In contrast, the nmol of dipalmitoyl-PtdCho formed by cofactor-independent transacylation remains nearly the same after short-time and longer incubation. The nmol of dipalmitoyl-PtdCho formed by CoA-mediated transacylation increased strongly in the same time interval. Beside synthesis de novo via the CDP-choline pathway and reacylation of lyso-PtdCho with palmitoyl-CoA, the CoA-mediated transacylation of lyso-PtdCho may be an effective pathway for the formation of dipalmitoyl-PtdCho in pulmonary type II cells.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Cholesterol blood levels in children: comparison of a Munich screening to worldwide studies from 1980 to 1990.

Total cholesterol results of a screening of 134 Munich school children aged 6-11 years are described. In reviewing worldwide studies on blood lipids in children, in the last 10 years, I note a large variance in the so-called "normal" values, with mean levels of total cholesterol ranging from 148 to 214 mg%. Age-, sex-, and race-specific reference data for a population are needed. Only with these special data can one determine the point for intervention. With school health education programs, including medical screening examinations, the aim of primary prevention of coronary heart disease can be reached.

Age Factors↗
PubMed1991

Pattern of lipids associated with cytoskeletal protein prepared as Triton X 100 insoluble residues in some single cell types.

The cytoskeletal proteins from erythrocytes, lymphoid cells, unstimulated and stimulated platelets, HeLa cells, and Ehrlich ascites cells were prepared as Triton X 100 insoluble residues. The pellet was extracted using the Bligh-Dyer procedure. After separation of the lipids by thin-layer chromatography, phospholipids and neutral lipids were estimated and the lipid pattern was compared with the lipid composition of the total cell. The percentage of the lipids associated with the Triton X 100 insoluble pellet ranged between 10 and 50 depending on the lipid and the cell type. Despite of the heterogenous protein composition of the residue in the different cells involving microfilaments and intermediate filaments together with associated proteins and minor components, in all cells sphingomyeline (Sph) and free fatty acids (FA) could be found in outstanding contents. In HeLa cells we found beside the high proportion of Sph a different species pattern of diacyl-, alkylacyl-, and alkenylacyl classes of endogenous diacylglycerol (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). The discussion involved the data from literature showing lipid associations with all 3 classes of cytoskeletal filaments: microtubules, intermediate filaments, and microfilaments. These results were obtained by histological observation, by in vitro binding studies between cytoskeletal proteins and purified lipids, and--as we have practised--by lipid analysis after extraction of the more or less purified cytoskeleton. Artefacts could not be excluded, but the different lipid pattern in the total cell compared with the cytoskeletal let us assume that the results can not be explained by coprecipitation of micelles or organelle remnants with the Triton X 100 insoluble residue alone. An in vivo association of lipids, mainly of Sph, with F-actin and/or associated proteins might be concluded.

Actin Cytoskeleton↗
PubMed1989

Species pattern of phosphatidic acid, diacylglycerol, CDP-diacylglycerol and phosphatidylglycerol synthesized de novo in rat liver mitochondria.

Rat liver mitochondria were incubated with [3H]glycerol 3-phosphate, ATP, CTP and coenzyme A allowing acylatin of glycerophosphate with endogenous fatty acids and the further conversion of labelled phosphatidic acid (PA) to diacylglycerol (DG), CDP-diacylglycerol (CDP-DG) and phosphatidylglycerol (PG). In these glycerolipids, the distribution of label among the individual molecular species was found to be similar, with 16:0-18:1, 16:0-18:2 and 18:0-18:2/16:0-16:0 being the main species. It was concluded that mitochondrial enzymes involved in the de novo synthesis of these glycerolipids exhibited no acyl selectivity for their substrates. The pattern of molecular species of mitochondrial PA, DG and CDP-DG closely approached that of the same glycerolipids synthesized de novo in isolated rat liver microsomes.

Animals↗
PubMed1989

Synthesis of phosphatidylcholine and phosphatidylglycerol in rat lung mitochondria.

The mitochondrial fraction of adult rat lung contains choline phosphotransferase (EC 2.7.8.2) activity which can not be explained by microsomal contamination estimated on the basis of marker enzyme distribution. Mitochondrial (14C)glycerol-3-phosphate incorporation into PC (phosphatidylcholine) can be distinguished from the microsomal incorporation by different sensitivity to N-ethylmaleimide inhibition. The data indicate that rat lung mitochondria have the intrinsic capability to synthesize PC. Both synthesis of PC and PG (phosphatidylglycerol) are susceptible to isotonic tryptic attack against the cytoplasmic face of isolated rat lung mitochondria, suggesting the outer membrane location of crucial activities involved in the formation of these phospholipids. Rat liver mitochondria are different from rat lung mitochondria with respect to their capability to synthesize PC, their rate of (14C)glycerol-3-phosphate incorporation into PG as well as the submitochondrial site of PG formation.

Animals↗
PubMed1989

The de novo synthesis of molecular species of phosphatidylinositol from endogenously labeled CDP diacylglycerol in alveolar macrophage microsomes.

The de novo synthesis of molecular species of phosphatidylinositol (PI) from endogenously labeled CDP diacylglycerol (CDP-DG) and phosphatidic acid (PA), with [14C]-glycerol 3-phosphate, in microsomes of macrophages was studied using a recently developed HPLC technique. Endogenously labeled PA, CDP-DG, and PI were sequentially formed from labeled glycerol 3-phosphate through the addition of CoA, CTP, and then inositol into microsomes. The rate of formation of CDP-DG from endogenously labeled PA was low as compared with those of PA and PI. The low rate of CDP-DG synthesis suggests that it may be the rate-limiting step in the de novo synthesis of PI. Analysis of newly synthesized molecular species of PI by HPLC revealed that large proportions of radioactivity were associated with the 16:0-18:1, 16:0-18:2, 18:1-18:2, and 18:2-18:2 species, and a small amount, 2-3%, of radioactivity was associated with the 18:0-20:4 species. The profiles of newly synthesized PA and CDP-DG species were quite similar to those of PI species. This suggests that the enzymes involved in the formation of PI species from glycerol 3-phosphate show little specificity toward different molecular species of substrates. The results of the present study also suggest that free fatty acid composition in microsomes greatly affect the composition of the molecular species of PI synthesized through the de novo pathway, since the proportion of fatty acids utilized for the de novo synthesis of PI species was similar to that of free fatty acids in the microsomal membrane.

Adenosine Triphosphate↗
PubMed1988

Species pattern of phosphatidylinositol from lung surfactant and a comparison of the species pattern of phosphatidylinositol and phosphatidylglycerol synthesized de novo in lung microsomal fractions.

1. Phosphatidylinositol (PI) is a minor component of lung surfactant which may be able to replace the functionally important phosphatidylglycerol (PG) [Beppu, Clements & Goerke (1983) J. Appl. Physiol. 55, 496-502] without disturbing lung function. The dipalmitoyl species is one of the main species for both PI (14.4%) and PG (16.9%). Besides the C16:0--C16:0 species, the C16:0--C18:0, C16:0--C18:1, C16:0--C18:2 and C18:0--C18:1 species showed comparable proportions in the PG and PI fractions. These similarities of the species patterns and the acidic character of both phospholipids could explain why surfactant PG may be replaced by PI. 2. PI and PG were radiolabelled by incubation of microsomal fractions with [14C]glycerol 3-phosphate (Gro3P). For 11 out of 14 molecular species of PI and PG we measured comparable proportions of radioactivity. The radioactivity of these 11 species accounted together for more than 80% of the total. The addition of inositol to the incubation system decreased the incorporation in vitro of Gro3P into PG and CDP-DG (diacylglycerol) of lung microsomes (microsomal fractions), but did not change the distribution of radioactivity among the molecular species of PG. These results supported the idea that both acidic surfactant phospholipids may be synthesized de novo from a common CDP-DG pool in lung microsomes.

Acylation↗
PubMed1988

Comparison of the HPLC-separated species patterns of phosphatidic acid, CDP-diacylglycerol and diacylglycerol synthesized de novo in rat liver microsomes (a new method).

The species pattern of phosphatidic acid was compared with that of CDP-diacylglycerol and diacylglycerol synthesized de novo by glycerol 3-phosphate acylation in a CoA ester-generating system in liver microsomes. The similarity of the species patterns of phosphatidic acid and CDP-diacylglycerol indicated that the CTP-phosphatidyl cytidylyltransferase showed no selectivity for individual species of its phosphatidic acid substrate. Since the species pattern of diacylglycerol deviated from that of phosphatidic acid, a slight acyl selectivity of the phosphatidic acid phosphohydrolase or a slight inhomogeneity of its substrate pool might be assumed. For the determination of the molecular species of CDP-diacylglycerol, a new method was developed. By incubation of CDP-diacylglycerol with oligonucleate 5'-nucleotidohydrolase (phosphodiesterase), phosphatidic acid was produced. The CDP-diacylglycerol-derived phosphatidic acid was methylated with diazomethane and then separated by reverse-phase HPLC in 15 molecular species.

Animals↗