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Biomedical subjects

C Kuhn

Publications and source records attributed to C Kuhn.

At least 163 records · Page 9Linked to original sources
PubMed1983

Degradation of elastin in experimental elastase-induced emphysema measured by a radioimmunoassay for desmosine.

Experimental emphysema, produced by a single intratracheal injection of elastase in hamsters, progresses in severity over months. To investigate whether this progression is due to continuous elastolysis, we measured the urinary excretion of desmosine by radioimmunoassay (RIA) as a measure of elastin catabolism in vivo. Normal hamster excreted 1.6 microgram of desmosine, equivalent to a daily turnover of approximately 0.4 mg of elastin. During the first 24 hr after injection of 25 units of elastase, excretion of desmosine was increased threefold, rapidly returning to normal over several days. Desmosine excretion was normal after 6 days. Homogenates of lungs from elastase-injected hamsters were incubated in vitro, and the release of soluble desmosine was followed by RIA as a measure of the active elastase in the tissue. The method was sufficiently sensitive to detect 0.1 microgram of enzyme bound to elastin. Desmosine solubilized in vitro from lungs removed at intervals after elastase injection was 10-fold that of control at 1 hr and slightly elevated at 48 hr, but equaled control levels at 7 days. These results indicate that the late progression of elastase-induced emphysema is not accompanied by increased elastolysis.

Amino Acids↗
PubMed1982

[Nephrotic syndrome as indication for one-stage bilateral renal embolisation (author's transl)].

A 42-year-old patient suffered from a nephrotic syndrome due to primary perireticular amyloidosis. One year after diagnosis the renal protein loss increased to 40 g/d within a short time so that sufficient substitution was no longer possible. The creatinine clearance was 7-10 ml/min so that haemodialysis was performed as a vital measure to remove excessive fluid. Two weeks later, as an alternative to surgical bilateral nephrectomy, simultaneous bilateral renal embolisation with Ethibloc was done without complications. A small artery to the left lower pole was spared from embolisation. Computer tomographic follow-up showed a residual parenchymal perfusion in the subcapsular and left lower pole areas so that metabolic functions of the renal parenchyma persisted. Plasma renin activity decreased to subnormal levels, the erythropoietin plasma level remained in the lower range of normal. "Medical binephrectomy" should be considered more often as a therapeutic alternative to surgery in therapy-resistant nephrotic syndrome on account of its advantage of preserved metabolic renal function.

Adult↗
PubMed1982

Formation of cytoskeletal elements during mouse embryogenesis. III. Primary mesenchymal cells and the first appearance of vimentin filaments.

The cytoskeletal composition of the 'primitive streak' stage of mouse embryos, i.e. at late day 8 ('day 8.5') of gestation, has been examined by electron microscopy, using thin sections of fixed and embedded embryos, and by immunofluorescence microscopy, using cryostat sections of frozen embryos. At this stage primary mesenchymal cells are observed in the posterior part of the embryo which seem to migrate toward the anterior region. For most of the embryo, these mesenchymal cells are separated from the embryonic ectoderm by a continuous basal lamina. Frequently mesenchymal cells form cytoplasmic projections many of which make contact with this basal lamina, with surfaces of proximal endoderm cells, or with other mesenchymal cells. Primary mesenchymal cells contain sparse individual intermediate-sized filaments (IF), but closely packed IF bundles as they occur as tonofibrils in both embryonic epithelia, ectoderm and proximal endoderm, have not been found. Mesenchymal cells also can form junctions of the fascia adhaerens-type but appear to be devoid of desmosomes. Antibodies to cytokeratins reveal strong fibrillar fluorescence in cells of the proximal endoderm and weak, predominantly subapical staining in embryonic ectoderm. Correspondingly, antibodies to desmoplakins, the major proteins of the desmosomal plaque, show punctate fluorescence in both embryonic epithelia. These epithelial cells are not significantly stained with antibodies to other IF proteins such as vimentin and desmin. However, antibodies to vimentin show positive fluorescence, often in fibrillar tangles, in primary mesenchymal cells which in turn are negative with cytokeratin and desmin antibodies. This first detection of expression of vimentin in embryogenesis has been confirmed by two-dimensional gel electrophoresis of cytoskeletal proteins from 35S-methionine-labelled embryos. The observations indicate that during embryogenesis synthesis of vimentin occurs, for the first time, in the primitive streak stage and is restricted to the primary mesenchymal cells. Concomitantly, these cells cease to produce cytokeratins and desmoplakin. Possible mechanisms effective in this rapid change from epithelial to mesenchymal character, i.e. from cytokeratin IF to vimentin IF, are discussed.

Animals↗
PubMed1982

Effects of hydrocortisone acetate on pulmonary alveolar macrophage colony-forming cells.

We investigated the effect of prolonged monocytopenia induced by daily injections of hydrocortisone acetate on the number of alveolar cells and alveolar macrophage colony-forming cells (AL-CFC) in mice. We did not observe an appreciable reduction in the number of either alveolar macrophages of AL-CFC under this experimental condition, which markedly inhibited the blood monocyte concentration over 10 days. These results suggest the existence of a mechanism by which the number of alveolar macrophages, including AL-CFC, can be maintained without a continuous migration of blood monocytes into alveolar spaces.

Administration, Topical↗
PubMed1982

Bleomycin-induced pulmonary fibrosis in hamsters: effect of neutrophil depletion on lung collagen synthesis.

The development of pulmonary fibrosis in hamsters after the intratracheal instillation of bleomycin is attended by exudation of polymorphonuclear leukocytes (PMNs), but the function of these cells is unknown. In this study, we examined the effect of PMN depletion on lung collagen synthetic rate in bleomycin-treated hamsters. Antiserum to hamster PMNs was produced in rabbits and injected intraperitoneally into hamsters on the fourth through seventh days after intratracheal instillation of bleomycin or saline. Control animals received either normal rabbit serum (NRS) or no serum. Anti-PMN serum (APS) significantly reduced PMN exudation after bleomycin treatment through the eighth day (p less than 0.01). Collagen synthetic rate measured in lung explant cultures was increased in all bleomycin-treated groups compared with that in the saline injected control group (p less than 0.005). Collagen synthesis was greater in neutrophil-depleted bleomycin-treated hamsters than in bleomycin-treated animals receiving NRS or no serum on Days 8 (p less than 0.01) and 12 (p less than 0.05). In APS-treated hamsters, the proportion of protein synthesis directed toward collagen synthesis was increased above other bleomycin-treated groups, suggesting that collagen synthesis is selectively increased in neutrophil-depleted hamsters with bleomycin-induced pulmonary fibrosis.

Animals↗
PubMed1982

The effect of oxygen on Cor pulmonale in experimental emphysema induced by elastase or elastase and beta-aminopropionitrile in hamsters.

Right ventricular hypertrophy in elastase-induced emphysema in the System hamster was assessed by either the weight of the right ventricle as a fraction of body-weight or by the ratio of the weight of the right to the left ventricle. Right ventricular hypertrophy accompanies elastase-induced emphysema and is more severe in hamsters injected with elastase while fed a diet containing 0.5% beta-aminopropionitrile (BAPN), a combination that causes more severe emphysema. Measurements of arterial blood oxygen pressures showed that emphysematous animals were hypoxemic. Treatment of emphysematous animals with 35% O2 either during the development of right ventricular hypertrophy or after it had developed produced measurable amelioration of the hypertrophy in those groups with the more severe emphysema (elastase plus BAPN diet) but did not completely prevent it. The oxygen had no effect on the severity of the emphysema measured morphometrically. These results indicate that the cor pulmonale in elastase-induced emphysema is probably multifactorial, but hypoxia appears to be one of the major factors.

Aminopropionitrile↗
PubMed1982

Elastase of U-937 monocytelike cells. Comparisons with elastases derived from human monocytes and neutrophils and murine macrophagelike cells.

As an approach to facilitating the understanding of proteinases associated with monocytes we have studied U-937 monocytelike cells. Elastase activity was identified in U-937 cell extracts and compared to monocyte elastase activity, neutrophil elastase, and the elastase activity from a continuous line of murine macrophagelike cells (P388D1). Serine proteinase activity which solubilized (14)C-labeled elastin accounted for >90% of the neutral proteinase activity of both U-937 cells and monocyte extracts. U-937 cell and monocyte elastase activities were similar catalytically, resembling neutrophil elastase. U-937 cells and monocytes showed other similarities: (a) both had activities reacting with [(3)H]diisopropylfluorophosphate that migrated in sodium dodecyl sulfate (SDS) polyacrylamide gels at approximately 30,000 and 60,000 daltons and (b) both contained material that cross-reacted with antiserum raised to neutrophil elastase. Preliminary characterization of U-937 cell elastase activity by affinity chromatography and ion-exchange chromatography suggested the presence of at least two distinct elastases. Minimal elastase activity was found in U-937 cell-conditioned medium, indicating that the activity is not spontaneously released by the cells. In contrast to the elastase activity associated with U-937 cells and monocytes, the elastase activity associated with P388D1 cells was a metalloproteinase and was found principally in the culture medium. These results indicate (a) U-937 cells will be useful for further investigation of proteinases associated with normal monocytes; (b) monocytes and U-937 cells contain material with catalytic and immunologic similarities to neutrophil elastase; (c) monocyte elastase activity differs from elastase activity secreted by murine macrophages and murine macrophagelike cells of the P388D1 line.

Amino Acid Chloromethyl Ketones↗
PubMed1982

Structure and function of the hepatitis B virus genome.

A preliminary map of the hepatitis B virus genome has been derived from the nucleotide sequence of cloned human hepatitis virus (HBV) DNA. The genes for two viral antigens were identified and their expression was studied using SV40 vector systems. HBV DNA cloned and amplified in bacteria induces hepatitis in chimpanzees demonstrating that the cloned HBV DNA is functionally intact.

Base Sequence↗
PubMed1981

Human alveolar macrophage fibronectin: synthesis, secretion, and ultrastructural localization during gelatin-coated latex particle binding.

Human pulmonary alveolar macrophages synthesized and secreted several characteristic high molecular weight proteins for at least 7 d in vitro. Immunoprecipitates of medium and cell lysates from metabolically labeled cultures with specific anti-human plasma fibronectin IgG contained one major labeled polypeptide of molecular weight 440,000 (unreduced) or 220,000 (reduced). An identical polypeptide in conditioned medium from radiolabeled macrophages bound specifically to gelatin-Sepharose, demonstrating that alveolar macrophages synthesized and secreted a molecule immunologically and functionally similar to fibronectin. Fibronectin was the major newly synthesized and secreted polypeptide of freshly harvested alveolar macrophages. Pulse-chase experiments revealed that newly synthesized fibronectin was rapidly secreted into medium, approximately 50 percent appearing by 1 h and 80 percent by 8 h. Immunoperoxidase staining using antifibronectin F(ab')(2)-peroxidase conjugates revealed the majority of immunoreactive fibronectin to be intracellular, localized to endoplasmic reticulum and Golgi apparatus. No extracellular matrix fibronectin was visualized, and cell surface staining was rarely seen, usually appearing only at sites where cells were closely apposed and not at sites of macrophage-substrate attachment. Similar immunostaining of fibroblast cultures revealed cell surface-associated fibrillar fibronectin. Ultrastructural localization of fibronectin during binding and phagocytosis of gelatin-coated and plain latex particles revealed fibronectin only on gelatin-latex beads and at their cell binding sites. Neigher plain latex beads nor their cell membrane binding sites stained for fibronectin. These results demonstrate that fibronectin is a major product of human alveolar macrophages, is rapidly secreted, and is localized at cell membrane binding sites for gelatin-coated particles. In view of the known binding properties of fibronectin, it may serve as an endogenous opsonic factor promoting the binding of staphylococcus, denatured collagen, fibrin, or other macromolecules to macrophages in the lower respiratory tract.

Cell Membrane↗
PubMed1981

Congenital alveolar capillary dysplasia--an unusual cause of respiratory distress in the newborn.

The clinical and anatomical features of a patient with an unusual pulmonary malformation, is reported. The clinical course was consistent with the syndrome of persistent fetal circulation; morphologically, however, the patient was found to have a unique form of pulmonary dysplasia. Failure of formation and ingrowth of alveolar capillaries led to absence of normal air-blood barriers in this term infant. In addition anomalous veins were present in the bronchovascular bundles. Morphometric study indicated that the lungs were otherwise mature. This selective deficiency and dysplasia suggests that distal pulmonary epithelial and vascular development operate under separate control mechanisms.

Abnormalities, Multiple↗
PubMed1980

111Indium-labeled human alveolar macrophages and monocytes: function and ultrastructure.

Human alveolar macrophages and peripheral blood mononuclear cells were labelled with indium-111 (111In)-oxine in ethanol. The efficiency of labeling averaged 84% for macrophages and 74% for mononuclear cell preparations. Phagocytosis by macrophages, the release of colony stimulating factor activity (CSF) by macrophages, and chemotaxis by monocytes in response to human C5-derived chemotactic factor (C5fr) and formyl-methionyl-leucyl-phenylalanine (f-MLP), were indistinguishable between labeled and unlabeled cells. Microscopically, labeled cells looked similar to control cells. Radioautography demonstrated 111In throughout the labeled cells, but there was a disproportionately high quantity over nuclei. These findings add to the growing literature indicating that 111In labels cells efficiently and that cells can retain function after being labeled with 111In.

Autoradiography↗
PubMed1980

Modification of PM2 DNA with N-acetoxy-2-acetylaminofluorene: changes in buoyant density, electrophoretic mobility and electron microscopic structure.

PM2 DNA, forms I and II, were chemically modified with the ultimate carcinogen N-acetoxy-2-acetylaminofluorene. The products were subjected to 3 analytical procedures: (i) buoyant density centrifugation in the presence of the intercalating dyes ethidium bromide or propidium diiodide; (ii) agarose gel electrophoresis: and (iii) electron microscopy. It was found that carcinogen-modified DNAs banded at higher densities in the presence of either dye. This effect was far more pronounced with form I DNA than with form II. Form I DNA showed a concentration-dependent decrease of migration velocity in agarose gel electrophoresis after modification; form II DNA exhibited a similar but smaller effect. Electron microscopy of form I DNA did not reveal a consistent correlation between the extent of chemical modification and the loss of superhelical turns. Form II DNA exhibited characteristic alterations such as aggregation of several PM2 molecules into network-like structures, kinky configuration, and probably single-stranded bubbles extending over 600-1500 bases.

2-Acetylaminofluorene↗
PubMed1980

The effect of lathyrogens on the evolution of elastase-induced emphysema.

When pancreastic elastase is introduced into the lungs of hamsters to produce emphysema, there is an initial rapid destruction of elastin followed by a subsequent resynthesis. In order to investigate its pathologic significance, we attempted to interfere with this resynthesis by feeding inhibitors of elastin cross-linking. The feeding of the lathyrogens beta-aminoproprionitrile (beta APN) or penicillamine resulted in a marked worsening of the elastase-induced emphysema, as measured by the average distance between alveolar walls and the internal alveolar surface area, when compared with the effect of elastase in animals fed a normal diet. The lathyrogens produced no effect on lung morphology without elastase injections. In elastase-injected animals, the principlal biochemical effect of beta APN was a decrease in the aldehyde content of the elastin without a measurable decrease in desmosine cross-links. These results indicated that the formation of normal connective tissue proteins during the replair of elastolytic injury helps to limit the degree of anatomic deformity that is produced.

Aminopropionitrile↗