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Biomedical subjects

I Mandl

Publications and source records attributed to I Mandl.

18 recordsLinked to original sources
PubMed1987

Decreased elastic fibers and desmosine content in incompetent cervix.

Incompetence of the uterine cervix is a syndrome of painless, progressive dilatation and effacement occurring between the sixteenth and twenty-fourth weeks of gestation that represents abnormal functioning. It may serve as a model to elucidate normal function. Because the incompetent cervix results in painless opening of this organ without uterine contraction before term gestation, it is considered one of the causes of midtrimester spontaneous abortion, habitual spontaneous abortion, and early preterm labor. Untreated, it leads to rapid expulsion and often death of the fetus. We used light microscopy to compare decreased elastic fibers in incompetent cervices with those of normal nonpregnant and pregnant cervices. Morphologic analysis of this difference was extended to biochemical quantification of elastin content in one patient with cervical incompetence. The decrease in elastin suggests that one function of cervical elastin may be to maintain a closed and undilated cervix throughout gestation. There may be a relationship between changes in cross-linked elastin and the incompetent cervix; further studies are therefore indicated.

Amino Acids↗
PubMed1987

Increased synthesis of elastin in amiodarone-induced pulmonary fibrosis.

Both synthesis and total content of lung elastin were measured after induction of interstitial pulmonary fibrosis in hamsters by a single intratracheal insufflation of amiodarone. Elastin synthesis, as measured by 14C-lysine incorporation into desmosine and isodesmosine, was significantly elevated (P less than 0.05) above control values for a 3-week interval after induction of lung injury. Total lung elastin content in the amiodarone-treated animals was 32% greater than in controls (P less than 0.05) 2 weeks after insufflation of the agent. Furthermore, the time course of elastin synthesis in this experimental model was similar to that observed in bleomycin-induced pulmonary fibrosis in hamsters. Increases in elastin may therefore be a common feature of interstitial pulmonary fibrosis and may contribute to the altered lung mechanics seen in this disease.

Amiodarone↗
PubMed1986

The fibronectin content of canine lungs is increased in bleomycin-induced fibrosis.

Fibronectin (Fn), a high molecular weight glycoprotein, was found to constitute 0.43% of the normal adult beagle dog lung. The tissue Fn (TFn) was solubilized by sequential chemical extractions and quantified by ELISA (enzyme-linked immunoabsorbent assay). Subsequent plasmin digestion did not appear to solubilize significantly more Fn. Since 70% of the lung tissue was solubilized by the extractions and plasmin digestions, the TFn quantified represented the bulk of lung Fn. The TFn was identical to plasma fibronectin in the ELISA and one can infer that the Fn molecule is not significantly altered as it is incorporated into the lung connective tissue matrix. Lungs from beagles in which fibrosis had been induced with bleomycin contained 0.99% Fn, more than a twofold increase over normal. In the ELISA TFn from fibrotic lungs gave an inhibition curve of the same shape as did TFn from normal lungs. Thus, Fn from fibrotic lungs is not different qualitatively from Fn from normal lungs in any way detectable with this antiserum. The TFn content of plasmin digests of intact lung was less than that of extracts, which was the converse of results obtained on placenta (B. A. Bray (1985) Biochem. J. 226, 811-815). This difference between lung TFn and placental TFn may be due to differences in degree of glycosylation, which determines susceptibility to proteases.

Animals↗
PubMed1985

Stimulation of lung lysyl oxidase activity in hamsters with elastase-induced emphysema.

Lysyl oxidase activity was measured in lung extracts of hamsters with elastase-induced emphysema 8 days after administration of the enzyme and again after 2, 3, and 4 wk. Levels of activity rose rapidly to 7 times the base values determined in the lungs of saline-injected control animals. In parallel with the increase in lysyl oxidase activity, the rate of 14C-lysine incorporation into desmosine and isodesmosine was at its maximum 1 wk after elastase administration, reflecting the lysyl-oxidase-mediated cross-link formation, which is the final step in the resynthesis of the pulmonary elastin destroyed by the elastolytic insult.

Amino Acid Oxidoreductases↗
PubMed1985

Impairment of elastin resynthesis in the lungs of hamsters with experimental emphysema induced by sequential administration of elastase and trypsin.

The nonelastolytic proteases trypsin and chymotrypsin were administered to hamsters 24 hours after intratracheal injection of elastase. Severity of the disease, extent of degradation and resynthesis, new cross-link formation, and the levels of the enzyme lysyl oxidase, which mediates the cross-link formation, were compared with the same parameters measured in hamsters with experimental emphysema induced by elastase alone. Increases in mean linear intercept indicated that a more severe form of the disease was produced. Although elastin degradation after 1 week was similar in both groups, resynthesis of the elastin destroyed by the elastolytic insult was significantly impaired in the animals injected sequentially with elastase and trypsin or chymotrypsin. Formation of new elastin as monitored by 14C-lysine incorporation into the elastin specific cross-links desmosine and isodesmosine was reduced approximately 40%, although there was no significant difference in the levels of lysyl oxidase activity. It is suggested that the most likely mechanism compatible with the recorded observations involves destruction of the microfibrillar component of the elastic fiber by trypsin or chymotrypsin, resulting in the absence of the requisite template for resynthesis of the pulmonary elastin.

Animals↗
PubMed1979

Characteristics of a clone of endothelial cells derived from a line of normal adult rat lung cells.

A strain of endothelial cells derived from a single cell cloned from a line of normal adult rat lung parenchyma has been maintained in tissue culture for more than 3 years. These cells have been identified as endothelial cells based on the combination of their growth characteristics, cell morphology as observed with both light and electron microscopy, and their physiological properties. They have continued to produce granules, which stain specifically for glycosaminoglycans with Alcian blue, for over 2 1/2 years. During the same period of time, glycosaminoglycans were identified biochemically in both cells and medium. They have maintained the ability to degrade bradykinin over this period as well.

Animals↗
PubMed1979

Alpha 1-antitrypsin deficiency and increased susceptibility to elastase-induced experimental emphysema in a rat model.

Administration of 200 mg of D-galactosamine/kg intraperitoneally to rats produced a decrease in the serum concentrations of trypsin and elastase inhibitory capacities. Induction of emphysema by intravenous injection of pancreatic elastase resulted in significantly increased severity of the disease in the animals depleted of alpha 1-antitrypsin. The degree of severity of the disease determined by mean linear intercept suggested a correlation with trypsin and elastase inhibitory capacities at the time of elastase injection.

Animals↗
PubMed1978

Antiserum to surface antigens as a marker for cultured rat lung endothelial cells (1).

Antibodies were developed in rabbits against an established line of endothelial cells from normal adult rat lung. Pre- and postimmunization sera were tested for antibody activity by the indirect immunofluorescence technique. Preimmunization serum failed to react with the endothelial cells, whereas the antibody titer of postimmunization serum from two rabbits was 1:512. Organ specificity and species specificity were assessed by absorbing the serum with packed dissociated cells from different organs of the rat and lung cells of other species. Only cells obtained from rat lung absorbed the antibodies completely. The antiserum showed some crossreactivity with the other cultured cells but the pattern of fluorescence was different. In the presence of complement the antiserum was found to be cytotoxic to cultured rat lung endothelial cells but not to the other crossreacting cells.

Animals↗
PubMed1975

Alpha1-antitrypsin concentration in amniotic fluid.

Concentrations of alpha1-antitrypsin were measured in 80 specimens of amniotic fluid collected at various stages of pregnancy. Levels remained relatively unchanged throughout gestation, with a median concentration of 10.0 mg/100 ml at 12-24 weeks, 18.7 mg/100 ml at 34-37 weeks, and 16.2 mg/100 ml, after the 37th week. In three instances where the infant developed RDS, the median concentration was 12.4 mg/100 ml.

Amniotic Fluid↗
PubMed1975

Glycosaminoglycans produced in tissue culture by rat lung cells. Isolation from a mixed cell line and a derived endothelial clone.

The glycosaminoglycans produced by a mixed cell line of normal adult rat lung and an endothelial clone derived from this line were isolated and examined. Cellulose acetate electrophoresis of media and cells before and after digestion with specific enzymes indicated that all the major glycosaminoglycans except keratan sulfate were synthesized by both cultures. Heparan sulfate and dermatan sulfate were found only in the cell fraction while hyaluronic acid was found in both the medium and the cell fractions. The chondroitin sulfates were isolated from the medium. The endothelial clone produced a 4:1 ratio of glucosamine to galactosamine in the medium from the fifth through thirteenth months of culture. The medium of the mixed cell line initially contained glycosaminoglycans with a glucosamine to galactosamine ratio of 2:1 but after approximately one year of culture, the ratio had changed to 4.6:1 suggesting that the culture contained predominatly endothelial cells.

Cell Fractionation↗