Biomedical subjects
Publications and source records attributed to L Hartmann.
A systematic study was undertaken to evaluate the urinary Tamm-Horsfall protein (THP), creatinine and total protein elimination in 76 normal subjects divided into five groups during the first 30 years of life. This shows that urinary THP flow, relating to body surface area, increases progressively up to adult age.
A quantitative and qualitative study of neutral and aminosaccharides in C 1-esterase inhibitor (C 1-INH), protein of the complement system, was performed. We observe a mixed glycosylation of the molecule with an N-glycosylated: O-glycosylated chain ratio of 1: 4. The loss of the inhibitory activity of the molecule in hereditary angioedema (O ANH) is associated with an O-glycosylation deficiency which differs according to the two molecular variants: C 1-INH (1 A) and C 1-INH (II) previously described.
The familial mediterranean fever (FMF) is an inherited, autosomal, recessive disorder which occurs predominantly but not exclusively in Sephardic Jews. It is characterized by a total increase of blood complement components, particularly C4, without any molecular anomaly and associated with an increase in other inflammatory proteins. With colchicine therapy, the symptomatology observed regresses or diminishes and onset of amyloidosis is prevented but the inflammatory and biochemical syndrome persists.
Affinity chromatography purification was combined with a radioimmunoassay for 'Tamm-Horsfall-like' glycoprotein. This enabled serum concentrations to be established and to demonstrate its presence in cerebrospinal fluid for the first time. This assay method used in different circumstances suggests a multifocal synthesis. Nevertheless, urinary Tamm-Horsfall glycoprotein so far must be distinguished from the serum or cerebrospinal fluid Tamm-Horsfall-like glycoprotein.
Direct evidence is given for the presence of glucose, mannose and galactose as the products of hydrolysis of hemoglobins A1a1, A1a2, A1b, A1c and A0. The presence of galactose cannot be explained by the earlier hypothesis of Amadori rearrangement and suggests the existence of further complex rearrangements. Monosaccharide content of the different hemoglobin components varies from 0.2-2.0 mol/mol of alpha beta dimer with an increase of 1.5-2.0-times in diabetic components. This increase is not accompanied by net charge differences, suggesting that additionally bound sugars are not responsible for the pI modification of these hemoglobins. The pattern of glucose, mannose and galactose ratio in normal individuals divides these hemoglobins into two classes, hemoglobins A1b, A1c and A0 (ratio 0.60:0.25:0.15) on one hand and hemoglobins A1a1 and A1a2 (ratio 0.40:0.40: 0.20) on the other. These findings suggest that diverse mechanisms for sugar binding might exist between these two classes of glycosylated hemoglobins. This difference disappears in diabetic components suggesting that the non-NH2-terminal sites are glycosylated in all components by a common mechanism. Increase in glucose at the expense of mannose and galactose, as observed in diabetics, could be an indicator of recent glycosylation.
The gas-liquid chromatographic measurement of urinary creatinine described in this paper employs methylation, the use of a diethylene glycol succinate stationary phase, an internal L-hydroxyproline standard and a temperature of 180 degrees C. The technique, which is specific and reproducible, is shown to be a reference method providing more precise and reliable results than a conventional colorimetric method. In addition, it can be used as a routine method because of its simplicity.
The well-known heterogeneity of normal and pathological immunoglobulins M was investigated in a study involving the characterization of their carbohydrate moieties. Oligosaccharide units were released from the native molecule by hydrazinolysis, and they were fractionated by affinity chromatography on a concanavalin A-Sepharose column to yield separate N-acetyl-lactosaminic-type and oligomannosidic-type structures. Further identification of these oligosaccharides was attempted by t.l.c. on silica gel and by determination of their monosaccharide compositions. A comparative study of the oligosaccharide units belonging to each population of immunoglobulin M was possible. Similarities were found in the occurrence of both types of oligosaccharide structures, and, in addition, a common double heterogeneity could be demonstrated for N-acetyl-lactosaminic-type structures: they could be resolved by affinity chromatography into bi-, tri- and tetra-antennary structures, and they also showed differences in N-acetylneuraminic acid content. Though some variations were observed in the exact composition of the oligosaccharide units within each population, it was possible to consider a representative oligosaccharide-unit composition of normal immunoglobulin M as a standard for comparison. On this basis a predominance of multi-antennary structures was observed in the more glycosylated pathological immunoglobulins M (10% carbohydrate content), whereas oligomannosidic structures were increased in pathological immunoglobulins M with a lower content of carbohydrates (7%). These variations are thought to reflect differences in the biosynthetic processing pathway of the carbohydrate units of the pathological immunoglobulins M or the enhanced expression of a molecular clone.
L Pyruvate kinase (LPK) is considered to be the major form in the liver. Two isozymes, LPK and MPK, have been localized in the isolated rat hepatocyte in vitro with an immunocytometric method. MPK is induced by insulin, which also creates a slight stimulation of LPK (at physiological doses) in both fed and fasted animals. Glucagon inhibits LPK in fed animals (the fasting rat is already in a situation of gluconeogenesis and this hormone is ineffective). MPK is insensitive to glucagon, regardless of the nutritional state of the animals. Each PK isozyme is thus controlled predominantly by one of the two hormones, corresponding to a sophisticated regulation of hepatic glycolysis and gluconeogenesis.
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A purification method for C1 esterase is described. The final product significantly improved the sensitivity and the specificity of the enzymatic measurement of its plasma inhibitor C1-INH or alpha 2-neuraminoglycoprotein (alpha 2-NGP) by esterolysis of a synthetic substrate N-acetyl-L-tyrosine ethyl ester (ALTEe). A comparative study was done between the chromatographed C1 esterase and the native serum euglobulins: qualitative and quantitative determination of the serum contaminants, enzymatic activity measurement of C1-INH in normal subjects and in patients suffering from hereditary angioneurotic oedema (OANH) as well as in therapeutical C1-inhibitor concentrates.
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In liver, L-type pyruvate kinase (LPK) was considered to be the major isozyme. Using an immunocytometric method, it was demonstrated that labeled LPK (LPK+) hepatocytes were largely influenced by the nutritional status of the Rat, as well as addition of glucagon in vitro. In the fed Rats, the percentage of LPK-hepatocytes remained stable for at least 90 min. This decreased to one half value in the fasted Rats. Addition of glucagon (114 nM) had no effect in fasted Rats, but decreased the percentage of LPK-hepatocytes to a half in the fed Rats. It was concluded that neoglucogenesis status (fasting or addition of glucagon in fed Rats liver cells) induced a fall in the percentage of LPK-hepatocytes.
Platelets of reserpinized rabbits, incubated in buffer containing tritiated 5-hydroxytryptamine (3H-5HT), have the ability to convert 3H-5HT into labeled compound(s) extractable with alkaline-chloroform. The bulk of the chloroform-extractable radioactivity showed a Rf value similar to authentic melatonin on silicagel thin-layer chromatography. The labelled product eluted with ethanol from the silicagel area where melatonin was suspected to reside was identified as melatonin by mass spectrometry and radioimmunoassay. Our in vitro experiments demonstrate that rabbit platelets are capable of converting 5-HT into melatonin apparently because they possess the enzymatic equipment necessary for this biosynthesis i.e. serotonin N-acetyltransferase and hydroxyindole-O-methyltransferase.
Plasma and urinary melatonin, testosterone and luteinizing hormones were radioimmunologically assayed in 26 male babies during the first year of life. The results show that plasma melatonin levels are low during the phase of postnatal elevation of testosterone and luteinizing hormones. They subsequently increase when testicular activity decreases. Urinary elimination of melatonin does not vary during this period, suggesting the existence of variations in the synthesis or utilization of melatonin.
It was known that with dietary and hormonal conditions the level of hepatic L pyruvate kinase (LPK) varied greatly. By immunochemical method we demonstrate in vitro insulinodependence of MPK in isolated hepatocytes. In hepatocytes of fasted Rats this effect was time and concentration dependent, but proinsulin was ineffective.
An analysis of cell membrane material present in circulating immune complexes isolated from normal human sera by precipitation with polyethylene glycol (PEG) has been performed with the platelet alloantigen PlA1 and rhesus antigen used as markers. PEG precipitates obtained from the sera of subjects of known PlA1 and rhesus phenotype were resuspended in buffer and analyzed as representative of circulating immune complexes (CIC). The consumption of anti-PlA1 serum by CIC was determined by immunofluorescence and by inhibition of sodium 51chromate release from PlA1-positive target platelets. With these two techniques, PlA1 alloantigen activity was detected in CIC. This finding suggests that at least some of the cell membrane material present in CIC is derived from platelets.
In healthy human livers, L pyruvate kinase (L PK) was detected by immunofluorescence and double labelling in hepatocytes and M PK was detected in bile duct epithelial cells. Numerous associations between isoenzyme type and hepatological lesion were observed. In 10 cases of ethanolic cirrhosis, L and M PK were simultaneously observed in the hepatocytes of regenerative nodules, as they were in biliary neoductules; fibrotic regions were L and M PK negative and the hepatocytes in the anastomosing plate system were almost exclusively L PK positive, as in normal subjects. In 12 hepatocarcinomas, cancer cells had a double L and M specificity with variations in the intensity of the M isoenzyme, while the stroma reaction was L and M negative. In five hepatoblastomas, the simultaneous presence of L and M PK was also observed, but the consistently marked intensity of M PK argues in favour of the embryonic nature of this type of cancer. The results suggest that mature, highly differentiated cells exclusively and specifically synthesize one isoenzyme. A double specificity in pathology reflects the dysfunctional state of the hepatic and biliary epithelial cells or a dedifferentiated state which may terminate with the appearance of a cancer.