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Biomedical subjects

G Lubec

Publications and source records attributed to G Lubec.

At least 271 records · Page 15Linked to original sources

Effect of tracheal suction on oxygenation, circulation, and lung mechanics in newborn infants.

Transcutaneous PO2, heart rate, and aortic blood pressure were measured i 10 mechanically-ventilated newborn infants to assess the degree and course of hypoxaemia, and to monitor the cardiovascular and respiratory changes during tracheal toilet. Five infants weighed less than 1250 (mean 994), g and 5 infants weighed greater than 1750 (mean 2216) g. During tracheal suction the TcPO2 fell from 68 +/- 27 (mean +/- SD) to 43 +/- 23 mmHg, and the heart rate from 144 +/- 8 to 123 +/- 25 beats/minute, but the blood pressure increased from 44 to +/- 24 to 49 +/- 24 mmHg. Hypoxaemia (TcPO2 less than 50 mmHg) occurred in 7 of 8 initially well-oxygenated infants when suctioned. The decrease in TcPO2 was similar for both groups of infants. It was greater in infants with controlled ventilation and an F1O2 greater than or equal to 0.8 than in infants with intermittent mandatory ventilation and an F1O2 less than 0.8. The TcPO2 fall correlated well with the TcPO2 during the control period but not during the time that the infants were disconnected from the respirator. A critical re-evaluation of routine tracheal toilet is needed.

Blood Pressure↗

Glomerular permeability for proteins of high molecular weight entrapped in liposomes.

The glomerular filtration barrier is known to be negatively charged. Previous experiments have shown the importance of the electrical charge for permeability. We looked for permeability characteristics of proteins entrapped in liposomes with negative and positive charge detecting that the positive charge enables the protein to pass the glomerular filtration barrier.

Animals↗

[Collagenolytic activity of neoplastic and rapidly proliferating normal tissue].

By means of a biological collagenase assay the activity of this protease was examined in 12 invasive adenocarcinomas of the colon and compared to that in 10 normal thymus tissue biopsies. Collagenolytic activity at dimensions of 10(-3) units/mm diameter tissue could be revealed in all carcinomas, which significantly (p less than 0.001) surpassed the also regularly detectable activity in thymi. While 0-Phenantrolin and D-Penicillamin totally inhibited lysis of each sample, EDTA and normal human serum, remarkably inhibiting collagenase of normal thymus, only were able to reduce the lysis by cancer at 19 and 23% in the average leading to enzyme: inhibitor imbalance in malignancy. It can be suggested that collagenolysis displayed by adenocarcinomas is derived from the tumor itself, and is different from that of normal thymus--a rapidly proliferating organ--by means of enzymatic quantity and quality.

Adenocarcinoma↗

[Basement membrane degradation by enzymes of the 8000-g-lysosome fraction from cervical cancer cells].

By means of immunoelectrophoresis and immunodiffusion after Ouchterlony the spectrum of lysosomal enzymes in the 8000-g-fraction of invasive cervical carcinoma cells and of normal human lymphocytes was investigated. A glomerulobasement membrane preparation (GBM) was used as substrate, and the action was characterized by inhibition studies. The proteases of cervical carcinoma cells and of lymphocytes caused a GBM degradation into identical antigenic pieces. While o-phenanthroline, 5-fluorouracil and HgCl2 showed no enzymatic inhibition, EDTA as well as aprotinine inhibited partially in all cases combined. EDTA and aprotinine totally stopped the reaction. While normal human serum revealed total inhibition of lysosomal enzymes of lymphocytes, the proteases of cervical carcinoma cells only were inhibited partially at all concentrations. This defective inhibitions is discussed concerning its in vivo significance for invasion.

Basement Membrane↗

Total glycosylated hemoglobin in mothers of large-for-gestational-age infants: a postpartum test for undetected maternal diabetes?

Total glycosylated hemoglobin has been evaluated postpartum using a colorimetric (thiobarbituric acid: TBA) method in 50 mothers of large-for-gestational-age (LGA) infants (greater than 90th percentile by weight). 30 women without potential risk factors for chemical diabetes who gave birth to appropriate-for-gestational-age (AGA) infants formed the control group. When compared to the control mothers, mean total glycosylated hemoglobin (TBA color) levels were significantly higher in the mothers of LGA infants (p less than 0.01). 4 of the latter had an abnormal oral glucose tolerance test (GTT) done within 5 days postpartum and significantly elevated glycosylated hemoglobin compared to mothers of LGA infants with normal GTT (p less than 0.001). Furthermore, a significant linear correlation was found for mothers of LGA infants between TBA color levels and each of the following: fasting serum glucose (p less than 0.001), 1-hour serum glucose (p less than 0.001), 2-hour serum glucose (p less than 0.001), and infant birth weight (p less than 0.05). Analysis of TBA color levels early postpartum might be an alternative method for detecting unsuspected chemical diabetes in pregnancy.

Birth Weight↗

Hormone-sensitive adenylate cyclase in glomerular cells: possible role for inflammatory diseases of the glomerulus.

Using the adenylate cyclase assay after Ross we examined hormone sensitivity of isolated glomerular cells. cAMP production was increased 1.3--1.6-fold by stimulation with isoproterenol, 1.5--1.8 times by prostaglandin E1 and 1.4--1.5 times by histamine. The isoproterenol reaction could be completely inhibited by propranolol, the histamine effect was abolished by the H2-blocking agent cimetidine. As control we applied sodium fluoride, which directly activates the catalytic adenylate cyclase unit, increasing the activity 1.8--2.7 times (depending on the method of homogenization). These findings could reflect some physiological or pathophysiological implications, which are discussed in the present report.

Adenylyl Cyclases↗

[Prematurity risk according to prematurity risk score and postpartal morbidity of the newborn infants (author's transl)].

Risk of premature birth was evaluated retrospectively in 610 women in the first days after delivery using the prematurity risk score published by Thalhammer 1973. The calculated risk of premature birth was compared than prospectively to postpartal morbidity of the newborn infants as determined by duration of hospital stay, incidence of respiratory distress syndrome, need of artificial ventilation and mortality. A positive correlation could be found between risk of premature birth and postpartal morbidity of the newborn infants especially in small premature infants with birthweights of 2000 grams and less. The same correlation existed also in two groups of infants out of two different obstetric clinics which showed the same distribution of prenatal risks and the same prenatal care frequencies. It clearly becomes evident that infants with the same prenatal risks but good prenatal care during pregnancy had much lower hospital stays, lower respiratory distress frequencies and lower mortality rates than babies delivered from pregnancies badly cared for. These prenatal care related differences in postpartum morbidity again were much more evident in infants out of lower birth weight classes.

Birth Weight↗

Glomerular basement membrane changes, HbAIc and urinary excretion of acid glycosaminoglycans in children with diabetes mellitus.

Glomerular basement membrane antigens excreted into urine, urinary acid glycosaminoglycans and hemoglobin AIc plasma levels were estimated in 18 diabetic children. In comparison to controls we detected significant differences, in that diabetics with changed (alpha-1-) mobility on immunoelectrophoresis revealed increased urinary acid glycosaminoglycan excretion (p less than 0.01) and elevated HbAIc concentrations in plasma (p less than 0.01). HbAIc levels and urinary glycosaminoglycans correlated significantly (r = 0.7, p less than 0.001). Increased glycosaminoglycans as well as increased blood glucose reflected by elevated HbAIc could lead to the biochemical glomerular basement membrane changes found on immunoelectrophoresis. The results suggest a metabolic hypothesis for the development of diabetic glomerulopathy.

Adolescent↗

Collagenase activity of cartilage in rats with experimental lathyrism: a model of bone diseases.

Collagenolytic activity was estimated in skin and joint cartilage of lathyritic rats by means of a biological assay. Lathyrism was induced by feeding beta-aminopropionitrile fumarate for six weeks, and the lathyritic state was confirmed by characteristic radiographic, histomorphologic and biochemical findings. Both tissues in lathyritic animals revealed significantly increased collagenolytic activity in comparison with those of the control animals. Studies were performed using ethylendiaminetetraactate and normal rat serum to determine the origin of inhibition of the collagenolytic system inhibition. Since both agents showed no inhibition of collagenolysis, the highly increased collagenolytic activity in lathyritic skin and joint cartilage appears not to be derived from polymorphonuclear cells nor from serum, but from the tissue itself. Elevation of collagenase activity may be important with respect to the increased neutral salt solubility of collagen and hydroxyproline excretion observed in experimental lathyrism.

Aminopropionitrile↗

Collagenolytic activity in hyperacute lung allograft rejection.

Six mongrel dogs were presensitized by full thickness skin grafts followed by orthotopic lung homotransplantation. Tissue explants of the hyperacutely rejected lung grafts were placed on the surface of a gel of native collagen. Collagenase activity was found in each specimen. Lungs of 10 untreated dogs served as controls. The collagenolytic system of the transplanted lungs was inhibited by EDTA only. No inhibitory effect was obtained by the inhibitor of bacterial collagenase, cysteine, and normal serum containing protease inhibitors. By means of inhibition studies it was tried to determine the origin of the collagenolytic activity. It is suggested that the enzyme effect is derived from the lysosomes of polymorphonuclear leukocytes. Collagenase of granulocytic origin seems to participate as mediator in the immunological reaction of hyperacute lung graft rejection.

Animals↗

[Urinary excretion of acid glycosaminoglycans and glomerular basement membrane antigens in patients with Alport's Syndrome (author's transl)].

Urinary excretion of acid glycosaminoglycans (AGAG) was estimated in 12 patients with Alport's syndrome (AS), 10 patients with idiopathic nephrotic syndrome and 10 healthy children. Comparing children with AS and healthy subjects or patients with idiopathic nephrotic syndrome, significant differences could be detected. Glomerular basement membrane antigen excreted into urine showed in 12 out of 12 patients with AS altered immunoelectrophoretic mobility into the beta-zone thus correlating with increased AGAG excretion. 10 patients with idiopathic nephrotic syndrome and 10 healthy children, showing normal AGAG excretion rates, presented normal glomerular basement membrane antigen with alpha-2-mobility.

Antigens↗

[Intracellular concentration of phenylalanine, tyrosine and alpha-amino butyric acid in 13 homozygotes and 19 heterozygotes for phenylketonuria (PKU) compared with 26 normals (author's transl)].

Intracellular concentrations for phenylalanine, tyrosine, alpha-amino butyric acid and 7 other amino acids (glycine, alanine, valin, cystin, methionine, iso-leucin, leucin) were measured in lymphocytes of 13 homozygotes and 19 heterozygotes for phenylketonuria as well as in lymphocytes of 26 normals. Intracellular concentrations for phenylalanine, tyrosine and alpha-amino butyric acid were significantly higher in homo- and heterozygotes than in normals (p less than 0,001--p less than 0,01). For the other 7 amino acids there were no or only questionable differences. Between homo- and heterozygotes there was no difference in any of the amino acids. Intracellular phenylalanine: tyrosine ratio was essentially the same in all three groups of individuals. There was no correlation between intracellular phenylalanine above or below 10 nmol/10(6) cells and IQ in heterozygotes. The same is true for phenylalanine: tyrosine ratio greater or smaller than 1. In Homozygotes there was no correlation between intracellular phenylalanine and age -- to whom DQ/IQ is correlated. There was no significant difference in intracellular phenylalanine between homozygotes with blood levels above and below 908 mumol/l (15 mg/100 ml) at the time of blood sampling and no correlation between intra- and extra-cellular phenylalanine concentrations. Among the 26 normals there were only 2 with intracellular phenylalanine above 10 nmol/10(6) cells, both showing phenylalanine loading test curves suspicious for heterozygosity. The results are discussed and important functions of the cell wall supposed. An abnormal unknown intracellular metabolite being the real noxious agent could explain the incomparably different degree of brain dysfunction in individuals with equal though elevated intracellular phenylalanine concentrations i.e. homozygotes and heterozygotes for PKU.

Aminobutyrates↗

Reduced susceptibility of nonenzymatically glucosylated glomerular basement membrane to proteases: is thickening of diabetic glomerular basement membranes due to reduced proteolytic degradation?

Glomerular basement membrane (GBM) preparations were enzymatically glucosylated and applied to proteolytic degradation by several enzymes. The split products were then characterized and quantitatively estimated by high pressure liquid chromatography. For this purpose, GBMs were isolated by a sieving and sonication method, incubated with glucose and digested with the proteases trypsin, chymotrypsin, papain, pepsin and a lysosomal preparation. Comparison of the concentrations of split products obtained by proteolytic degradation of normal and nonenzymatically glucosylated membranes showed a remarkable reduced susceptibility of the nonenzymatically glucosylated membranes, possibly due to steric hindrance or altered electrical charge of the glucosylated membrane proteins. This could be interpreted as an additional factor for accumulation of basement membrane material in the diabetic state, that not only increased basement membrane synthesis may occur but also reduced catabolism could possibly contribute to the diabetic changes.

Animals↗

Proteolytic degradation of the glomerular basement membrane and immunochemical characterization of split products.

Glomerular basement membranes (GBM) were isolated and subjected to enzymatic degradation with the protease trypsin (Serva), chymotrypsin (Serva), papain (Sigma), pepsin (Serva) and collagenase (Worthington) as well as a lysosomal preparation from glass adherent rat blood and peritoneal exudate cells. Split products were characterized by immunoelectrophoresis and cellulose acetate electrophoresis. Urine was obtained from healthy rats and rats with Masugi's experimental glomerulonephritis, dialyzed and concentrated and applied on immunoelectrophoresis, using anti-GBM antibody from rabbit. Urinary GBM split products from healthy and nephrotic rats showed two precipitation lines like digestion products obtained after chymotrypsin degradation. This finding was supported by characterizing individual antigenic degradation products obtained after inhibition of GBM degradation by the lysosomal preparation with ethylenediaminetetraacetic acid and Trasylol alone and in combination, as well as with o-phenanthrolin. It is concluded that GBM-antigens excreted into urine indicate limited digestion of GBM by chymotrypsin-type protease.

Animals↗

Evidence of H2 receptor activity on glomerular cells.

The role of histamine in physiological and pathological states has not been fully elucidated. In the pathological state histamine release can be induced by several mechanisms. The most frequent events are IgE-mediated release, complement-mediated release and release by chemical agents. During inflammation histamine is set free and contributes to the course of inflammatory processes, either enhancing or inhibiting inflammatory reactions. In order to look for a target in the glomerulum we examined H2 receptor binding to isolated glomerular cells using 3H-cimetidine as ligand. Two binding sites were detected, a low affinity site with a kD = 6.3 microM and a high affinity site exhibiting a kD = 0.18 microM. These findings are comparable to properties of 3H-cimetidine receptor binding to brain membranes.

Animals↗