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Biomedical subjects

U Gerlach

Publications and source records attributed to U Gerlach.

At least 55 records · Page 3Linked to original sources

Drug intoxication: influence of hemoperfusion on human plasma fibronectin.

Fibronectin is a glycoprotein belonging to the opsonic system and able to mediate phagocytosis by the reticuloendothelial system (RES). Severe intoxications are often followed by a diminished capacity of RES-clearance. Patients with severe drug intoxications have lower concentrations of fibronectin in plasma than healthy persons. Charcoal hemoperfusion lowers plasma fibronectin by an average of 4.7 mg/dl. Initial values below 15 mg/dl did not undergo a significant decrease in the case of hemoperfusion. Regarding these findings, determination of plasma fibronectin seems a useful parameter for monitoring RES function during treatment of drug-intoxicated patients by hemoperfusion.

Adolescent↗

[Treatment of acute liver failure by plasmapheresis].

Repeated plasmaphereses were done in 7 patients with acute hepatic failure (5 of them with coma stage IV and two with stage III). Acute liver insufficiency was induced by fulminant viral hepatitis in 4 cases, by drugs in one case, and was caused by a dystrophic exacerbation of liver cirrhosis in two further cases. Four of the 7 treated patients have survived. Beginning improvement of hepatic function was evidenced by an increase of factor VII and prothrombin in plasma. Significant lowering of bilirubin could be observed in all cases. While ammonia values decreased continuously in the four successfully treated patients while on plasmapheresis, the opposite behaviour was observed in the decreased patients. The influence of plasmapheresis on the pathologically altered aminoacid pattern in hepatic coma was investigated in two patients: Before treatment clearly to excessively increased values of methionine and aromatic aminoacids (phenylalanine and tyrosine) were seen. Branched-chain aminoacids leucine, isoleucine and valine were normal to moderately decreased. After termination of plasmapheresis methionine and aromatic aminoacids were significantly lower, branched-chain aminoacids were slightly below the initial values. Improvement of consciousness correlated with increase of the quotient (val+leu+ile)/(phe+tyr).

Acute Disease↗

[alpha 1-Antitrypsin phenotypes in patients with chronic liver diseases].

In a 25-year-old man we had observed the development of a liver cirrhosis leading to death from bleeding of oesophageal varices within two years. An alpha 1-antitrypsin defect (MZ-type) was detected post mortem both by serum analysis and by tissue examination. It is well documented that homozygote, e.g. SS- or ZZ-type, antitrypsin defects are frequently accompanied by liver fibrosis or cirrhosis. In 174 patients with alcoholic hepatitis or alcohol-induced cirrhosis we demonstrated the distribution of alpha 1-antitrypsin phenotypes using gel electrofocussing to clarify whether the heterozygote alpha 1-antitrypsin defect--which is accompanied only occasionally by a slightly reduced total concentration of the alpha 1-antitrypsin in the blood--has an increased incidence in such patients. Compared to the healthy population (MS-type 4.0%), we observed 9,8% MS-type in the described 174 patients. This simultaneous occurrence of a chronic, alcohol-induced liver disease with the genetic aberration of the alpha 1-antitrypsin phenotype pattern is too frequent to be attributed to mere chance and may be one cause of the increased incidence of chronic liver diseases within families documented by clinicians.

Adult↗

Connective tissue components of the normal and fibrotic human liver. II. Clinical aspects.

In this second part, clinical aspects of connective tissue metabolism in the liver will be described and two main aspects considered. The first is the possibility to monitor the activity of fibrosis by the use of metabolites and enzymes of connective tissue metabolism. In recent studies the qualification for this purpose of enzymes such as procollagen prolyl hydroxylase and lysosomal N-Acetyl-beta-glucosaminidase and the N-terminal peptide of procollagen type III has been tested. The serum activities or concentrations of these substances in patients with chronic active liver diseases increase in due relation to the histologically estimated activity of liver fibrosis. The second aspect deals with therapeutic approaches to fibrosis in the liver by using connective tissue specific agents. So far none of the antifibrotic substances such as proline analogues, colchicine, lathyrogens and penicillamine has been used in longer-term antifibrotic treatment.

Acetylglucosaminidase↗

[Progress in the diagnosis of chronic liver disease: diagnostic activity in liver fibrosis and cirrhosis].

The incidence of chronic liver disease has increased due to more wide-spread alcoholism. Unfortunately practically no success has been achieved as yet in treating the final stage--decompensated cirrhosis of the liver. A decisive factor for progression of this disease is connective tissue formation, that is to say fibrosis in the liver. Up to now fibrosis of the liver can be diagnosed only by biopsy, but there is no method available to estimate the degree of its activity and progression, which would allow a more precise prognosis in the individual case. Some studies done in recent years on this problem of assessing the degree of activity of fibrosis of the liver are reviewed; these studies deal with enzymes and metabolites of collagen metabolism in the serum, glycoproteins and proteoglycans derived from the connective tissue matrix. According to various studies the best indicator of the degree of activity of liver fibrosis seems to be N-acetyl-beta-glucosaminidase and procollagen-peptide type III in the serum.

Acetylglucosaminidase↗

[The significance of structural glycoproteins, demonstrated by the example of the fibronectins. Biochemical principles and clinical use].

Fibronectin, a structural glycoprotein on cell surfaces, appears in significant concentrations too in human blood plasma. Fibronectin influences cell interactions and cell growth and is an essential part of the extracellular matrix. The following review summarizes the biochemistry and function of fibronectin--or rather of fibronectins, bearing in mind the difference in protein structure between plasma fibronectin and cell surface fibronectin. Fibronectin is identical with one opsonin (alpha 2-opsonic glycoprotein). During shock and septicemia it undergoes a marked decrease. The diminished concentration in the plasma indicates a reduced function of the reticulo-endothelial system. A report is given on initial substitution trials.

Cell Membrane↗

[Clinical aspects and pathology of connective tissue metabolism of the liver].

Reactions in the connective tissue metabolism are of considerable importance in the pathophysiological process of diseases. It is from this aspect that new findings in chronic liver diseases are reported in the present paper. A report is given on cellular and extracellular pathological changes in connective tissue functions. Diagnostic and pharmacological methods undergoing continued development for controlling and influencing liver fibrosis are discussed.

Antifibrinolytic Agents↗

Identification of two granulocyte/macrophage colony-stimulating factors from porcine leukocyte cultures.

Granulocyte/macrophage colony-stimulating factors (CSF) were found in large-scale serum-free cultures of porcine blood leukocytes. The factors were concentrated from the conditioned culture medium of Concanavalin A-stimulated leukocytes using ammonium sulfate salting-out fractionation. The protein precipitate at 45-90% salt saturation contained two CSF types upon gel filtration on Sephadex G-100: One type was found to be active on mouse, but not on human bone marrow stem cells and had an apparent molecular mass of 85 000-100 000 Da; the other of about 40 000-45 000 Da stimulated both mouse and human bone marrow stem cells.

Animals↗

Connective tissue components of the normal and fibrotic liver. I. Structure, local distribution and metabolism of connective tissue components in the normal liver and changes in chronic liver diseases.

The first part of this review describes the chemistry, the occurrence and the metabolism of extracellular connective tissue components in the liver. The normal liver contains typical connective tissue proteins (collagens, structural glycoproteins and proteoglycans) not only in vessel walls, perivascular areas and in the capsule, but they occur also in small amounts in the parenchyma, mainly in the space of Disse along the sinusoidal walls. The "interstitial" collagens type I and III represent the major amount of collagen in the normal as well as in fibrotic liver, showing a relative increase of type III in fibrosis. Basement membrane collagens type IV and V as well as the cysteine-rich collagenous components "7 S collagen" and "short chain collagen" have been shown to occur in extracts prepared after limited pepsin digestion. In the normal liver, basement membrane collagen can hardly be detected within the parenchyma by immunofluorescence microscopy; increased occurrence, however, can be shown along the sinusoids even in early stages of chronic liver diseases. The glycoprotein fibronectin was shown to be distributed very similarly to collagens type I and III, whereas the basement membrane specific glycoprotein laminin is restricted to vessel walls and the epithelial layer of bile ductuli in the normal liver but is also found in the parenchyma in fibrosis. Occurrence of proteoglycans is increased in fibrosis: a change in the composition of glycosaminoglycans from mainly heparan sulfate in the normal to dermatan- and chondroitin sulfate in the fibrotic liver was observed. It is not yet clear which cell type is mainly responsible for increased connective tissue synthesis in fibrosis. The occurrence of cells resembling smooth muscle cells ("myofibroblasts") in connective tissue septa of fibrotic livers and the fact that similar cells which actively synthesize collagen grow from explants of fibrotic livers may indicate the significance of this cell type in the process of liver fibrosis.

Basement Membrane↗

[Reduced plasma fibronectin in patients with sepsis and shock (author's transl)].

Plasma fibronectin concentrations were determined in 16 patients with sepsis and shock. In all patients a definite decrease was observed during the course of the disease which did not correlate with coagulative function. Fibronectin in plasma rose to normal levels with improvement in the clinical picture. It is possible that plasma fibronectin indicates the functioning of the reticuloendothelial system.

Adult↗

Diagnostic significance of connective tissue enzymes.

In spite of the extensive literature, little is known of the diagnostic value of the enzymes of connective tissue metabolism. This review summarizes the available information and assesses the significance of enzyme measurements for the diagnosis of hereditary and nonhereditary connective tissue diseases, with emphasis being given to the roles of abnormal activities of collagenases and lysosomal glycosidases in the detection of fibrotic processes.

Acetylglucosaminidase↗