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Biomedical subjects

G Schmitz

Publications and source records attributed to G Schmitz.

At least 289 records · Page 16Linked to original sources
PubMed1980

The binding of Gold(I) to metallothionein.

The binding of gold(I) to metallothionein, MT, has been unambiguously established by the reaction of Na2AuTM with purified horse kidney MT. Zinc was displaced more readily than cadmium although the latter could be displaced using large Au/Cd ratios. The metal exchange reactions were complete within 2 hr of mixing. Further evidence that such reactions might be physiologically significant were obtained by studying in vitro metal displacements in the liver cytol of in vivo metal treated rats: When Na2AuTM was added to the cytosol of rats administered CdCl2 in vivo, zinc, copper and cadmium were displaced in 2/1/1 ratios from the metallothionein fraction. The zinc and cadmium displacement provide direct evidence that the gold was binding to MT. Addition of Cd+2 to liver cytosol of gold-treated rats resulted in displacement of copper and zinc, but not gold, from the MT fractions. When liver MT is prepared from rats exposed to Au or Cd, the Cd/protein ratio increased during the preparation, but the Au/protein ratio decreased. The Mt-bound metals account for 95% of the cytosolic Cd but only 15%-30% of the cytosolic gold in these studies. Thus, the nonspecific binding of gold to MT in vivo should be considered as one aspect in its equilibration among protein binding sites, which include, inter alia, metallothionein. Gold was found to coelute with zinc and cadmium in the MT fraction of rat kidney cytosol, when both Cd and Na2AuTM were administered to the rats. The possible significance of gold binding to MT in the treatment of rheumatoid arthritis--chrysotherapy--is briefly discussed.

Animals↗
PubMed1979

Bis(L-cysteinato)gold(I): chemical characterization and identification in renal cortical cytoplasm.

L-Cysteinatogold(I) was prepared by the reaction of L-cysteine with KAuBr4 in acidic media and its solubility determined from pH 4 to 10. The solubility at pH 7.4 and 37 degrees C is 1 microM. In the presence of excess cysteine, the solubility increases because of formation of bis(L-cysteinato)gold(I). The equilibrium-constant for formation of the bis complex is 2.1 +/- 0.4 X 10(-3), which at pH 7.4 CORRESPONDs to an apparant formation constant of 4.4 X10(4). The formation of the bis adduct was confirmed by chromatographic separation of the products of the reaction between [35S]-L-cysteine and Na2AuTM. This complex elutes with Kav = 1.15 which allows it to be distinguished from other gold thiolates that might form in vivo. The bis(cysteinato)gold(I) complex is shown to be present in kidney cytosol isolated from rats given Na2AuTM in vivo. When additional cysteine is added to the cytosol in vitro, the peak at 1.15 is increased, but if glutathione is added, the low molecular weight gold elutes at Kav = 1.00, which is taken as evidence for the existence of bis(cysteinato)gold(I) in the cytosol preparation. The amount of gold present as bis(cysteinato)gold(I) after 4 different dose schedules has been measured and found to increase with the total cytosol gold concentration. L-Cysteinatogold(I) does not dissolve in the presence of bovine serum albumin to form an adduct.

Animals↗
PubMed1978

[Muscle blood flow and capillary diffusion capacity in patients with rheumatoid arthritis (author's transl)].

Capillary blood flow (Xenon-133) and diffusion capacity for Chrom-51-EDTA (PS-Product of Renkin) of striated muscle tissue were examined by double isotope method in patients with rheumatoid arthritis. Xenon-Clearance and PS-Product were studied under normal conditions and following hyperemisation. There existed no significant difference between rheumatoid patients and normal subjects and there was no evidence of increased capillary permeability. Apparently, derangement of muscle capillaries is rare in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1978

The role of high density lipoproteins in lecithin:cholesterol acyltransferase activity: perspectives from Tangier disease.

Lecithin:cholesterol acyltransferase activity and the lipid composition of VLDL and LDL were examined in five patients homozygous for Tangier disease. The following results were obtained: I. The percentage of cholesterol that was esterified was similar in Taniger and control lipoproteins. II. Linoleic acid was the predominant fatty acid constituent of cholesteryl esters in Tangier plasma. III. Molar cholesterol esterification rates in Tangier plasma were reduced; however, fractional rates of cholesterol esterification were equal to or exceeded those of control plasma. IV. In vitro addition of apoprotein A-I and isolated lipoproteins led to a concentration-dependent increase in the initial rates of cholesterol esterification in Tangier plasma. It is concluded that HDL is not an exclusive substrate for the LCAT reaction, and that cholesterol esterification is not impaired in Tangier plasma.

Apolipoproteins↗
PubMed1978

Phosphatidylcholine substrate specificity of lecithin:cholesterol acyltransferase.

Lecithin:cholesterol acyltransferase (LCAT) has been partially purified by the combined method of ultracentrifugation and dextranblue-2000 4 B affinity chromatography. The enzyme was incubated with liposomes consisting of phosphatidylcholine-cholesterol in a molar ratio of 10/1. Chemically synthesized phosphatidylcholine substrates with labeled fatty acids in 1-and 2-position were chosen to evaluate the degree of transesterification. It was found that the fatty acid in the 1-position of phosphatidylcholine significantly influences cholesteryl ester formation, both by its direct involvement in the LCAT reaction and its contribution to the physico-chemical properties of phosphatidylcholine.

Chemical Phenomena↗
PubMed1976

[Guillain Barré- polyneuroradiculitis and Fisher-syndrome in cytomegalovirus infections (author's transl)].

In seven patients suffering from polyneuroradiculitis of the Guillain-Barré type and one case of Fisher syndrome, a cytomegalovirus infection was found. The elevation of the virus-specific IgM-antibodies was confirmed in all cases. The clinical course was severe and acute with respiratory disturbances, but complete remission occurred within 1-4 months. The complement fixing antibodies were highest during the first week of illness, so that further elevations could not be demonstrated, therefore making the IgM-antibody method of special importance. The role of cytomegalovirus infections in polyneuroradiculitis is also discussed.

Acute Disease↗
PubMedDate not supplied

Mevalonate is essential for growth of porcine and human vascular smooth muscle cells in vitro.

The effects of mevalonate depletion on growth and cell cycle kinetics of porcine and human vascular smooth muscle cells (SMC) were studied by growth curves and flow cytometric determination of cell cycle distribution. Porcine and human SMC were growth arrested by serum depletion for 48 h. Subsequently, they were stimulated to maximal growth and DNA synthesis by addition of serum. There was a concentration dependent decrease in the proliferation of human and porcine SMC, when cells were incubated in the presence of fluvastatin, a new, fully synthetic HMGCoA-reductase inhibitor. The reduction of cell number was significant with 10(-5) M and 10(-4)M fluvastatin. The highest concentration induced cell loss after prolonged incubation (> 4 days). The G/S-phase transition of human and porcine vascular SMC was reduced to 50% of controls by 10(-4) M fluvastatin as revealed by cell cycle analysis. The effects of fluvastatin on growth kinetics and cell cycle distribution could be completely reversed by the addition of 1 mM mevalonolactone. This indicates that the inhibitory effect of fluvastatin is caused by the inhibition of HMGCoA-reductase and depletion of mevalonate rather than being unspecific. Addition of LDL to supply cholesterol failed to support cell growth and transition of smooth muscle cells from G(zero)/G1-phase to S-phase, even though LDL was taken up by the cells as shown by confocal fluorescence microscopy. Neither did the addition of squalene or cholesterol to the culture medium normalize cell growth. It is concluded that nonsterol products that are synthesized from mevalonate are necessary for growth of smooth muscle cells. HMGCoA-reductase inhibitors like fluvastatin block the synthesis of these nonsterol precursors in human and porcine vascular SMC in vitro and are therefore growth inhibitory.

Animals↗
PubMedDate not supplied

Metabolic state of Zymomonas mobilis in glucose-, fructose-, and xylose-fed continuous cultures as analysed by 13C- and 31P-NMR spectroscopy.

The reasons for the well-known significantly different behaviour of the anaerobic, gram-negative, ethanologenic bacterium Zymomonas mobilis during growth on fructose (i.e. decreased growth and ethanol yields, increased by-product formation) as compared to that on its second natural substrate, glucose, have remained unexplained. A xylose-fermenting recombinant strain of Z. mobilis that was recently constructed in our laboratory also unexpectedly displayed an increased formation of by-products and a strongly reduced growth rate as compared to the parent strain. Therefore, a comprehensive study employing recently developed NMR-based methods for the in vivo analysis of intracellular phosphorylated pool sizes and metabolic fluxes was undertaken to enable a global characterization of the intracellular metabolic state of Z. mobilis during growth on 13C-labelled glucose, fructose and xylose in defined continuous cultures. The 13C-NMR flux analysis indicated that ribose 5-phosphate is synthesized via the nonoxidative pentose phosphate pathway in Z. mobilis, and it identified a metabolic bottleneck in the recombinant xylose-fermenting Z. mobilis strain at the level of heterologous xylulokinase. The 31P-NMR analyses revealed a global alteration of the levels of intracellular phosphorylated metabolites during growth on fructose as compared to that on glucose. The results suggest that this is primarily caused by an elevated concentration of intracellular fructose 6-phosphate.

Culture Media↗
PubMedDate not supplied

Dysregulation of lipid metabolism in Tangier monocyte-derived macrophages.

The cellular defect in Tangier mononuclear phagocytes (MNP) was shown to be associated with significant abnormalities in cellular phospholipid, triglyceride, and cholesteryl ester metabolism by using various radiolabeled precursors (32Pi, 3H-serine, 3H-choline, 14C-acetate, and 14C-oleic acid). Tangier MNP expressed increased rates of synthesis for phospholipids (twofold), triglycerides (fivefold), and cholesteryl esters (threefold) as compared to normal MNP when incubated in McCoy's medium containing 0.2% human serum albumin. The turnover rate of cellular phospholipids was also enhanced, while the turnover rates for triglycerides and cholesteryl esters were normal, thus leading to the accumulation of a larger pool of labeled triglycerides and cholesteryl esters in Tangier MNP. The individual phospholipid classes, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine were similarly affected. Cholesterol loading led to approximately 30% down-regulation of phospholipid synthesis in normal cells, but Tangier MNP showed a smaller response. When nonloaded normal MNP were exposed to high density lipoprotein3 (HDL3), they diminished cellular cholesterol esterification mediated by acyl-CoA:cholesterol acyltransferase (ACAT); in Tangier MNP, ACAT activity increased in the presence of HDL3. When cholesterol-loaded normal and Tangier MNP were treated with HDL3, an up-regulation of phospholipid synthesis was observed in both cell types, but Tangier MNP showed a smaller response. We conclude that the defect in Tangier disease, which we recently described as a "disorder of intracellular traffic" (Schmitz et al. Proc Natl Acad Sci USA 1985;82:6305-6309), is associated with a dysregulation of cellular lipid metabolism, leading to an overproduction of triglycerides and esterified cholesterol and to enhanced synthesis and catabolism of phospholipids.

Adult↗
PubMedDate not supplied

Abnormal processing of Golgi elements and lysosomes in Tangier disease.

It has been demonstrated that the cellular defect in Tangier disease is associated with morphological abnormalities in the lysosomal compartment and in the Golgi apparatus of mononuclear phagocytes (MNPs) after lipid loading by exposure to acetylated low density lipoproteins (acetyl-LDLs). On exposure to acetyl-LDL, Tangier MNPs accumulate two unusual types of vacuoles that were not observed in control MNPs. The electron-lucent type I vacuoles are round or ovoid, form aggregates, and are filled with fine flocculent or fibrillar material. Type II vacuoles are filled with more electron-dense material, are larger, and contain scrolls and lamellae with varying degrees of electron opacity. By immunoelectron microscopy both types of vacuoles could be identified as lysosomes. This abnormality of the lysosomal compartment in Tangier MNPs was not observed in Tangier fibroblasts, where the few lysosomes detected were found to be similar to those of controls. Morphological analysis of the Golgi apparatus in Tangier MNPs revealed numerous dilated Golgi cisternae, which were distributed more widely throughout the cell. However, both Tangier MNPs and especially Tangier fibroblasts showed a marked hyperplasia of the Golgi complex. Specific staining of the Golgi apparatus with the fluorescent ceramide analogue N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)]-6-aminocaproylsphingosine (C6-NBD-ceramide) showed that Tangier fibroblasts incorporated significantly higher amounts of C6-NBD-ceramide than did control fibroblasts. Moreover, the Tangier fibroblasts that appear generally larger than normal fibroblasts also show significant staining along the cytoskeleton, which may indicate the association of fluorescent ceramide and sphingomyelin to cytoskeletal elements. Phospholipid synthesis and catabolism were studied in Tangier fibroblasts from five patients with the use of tritiated choline as a tracer. A significantly higher incorporation rate was measured for sphingomyelin (176 +/- 18% of control) and phosphatidylcholine (144 +/- 12% of control). A moderate increase in catabolism was found for sphingomyelin (20 +/- 8% of control) and phosphatidylcholine (11 +/- 4% of control). These data are principally in agreement with our former studies of the abnormalities of phospholipid metabolism in Tangier MNPs (G. Schmitz et al, Arteriosclerosis 1990; 10:1010-1019). It is concluded that the defect in Tangier disease that we have recently described as a "disorder of intracellular traffic" (G. Schmitz et al, Proc Natl Acad Sci U S A 1985;82:6305-6309) is also expressed in Tangier fibroblasts. Tangier disease seems to be associated with morphological abnormalities of intracellular organelles, thus strongly indicating that the translocation disorder in this disease affects the Golgi apparatus and the regular processing of lysosomes and shows abnormalities in cellular lipid metabolism.

4-Chloro-7-nitrobenzofurazan↗