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Biomedical subjects

C Kuhn

Publications and source records attributed to C Kuhn.

At least 181 records · Page 10Linked to original sources

Lung collagen in type IV Ehlers-Danlos syndrome: ultrastructural and biochemical studies.

A patient with type IV Ehlers-Danlos syndrome developed recurrent pneumothoraces. At operation for poudrage of the pleura, an apical bulla was resected. Biochemical analysis of the lung tissue revealed increased solubilization of collagen by acetic acid extraction and by pepsin proteolysis. The relative proportion of type III collagen in the pepsin-solubilized collagen fraction was markedly decreased. Fibroblasts cultured from the patient's lung produced less type III procollagen relative to type I procollagen than control lung fibroblasts. Electron microscopic examination of the lung tissue showed dilated endoplasmic reticulum of the fibroblasts, and collagen fibers were normal. These observations suggested that the structural abnormalities in the lung that led to pneumothorax in this patient were due to deficiency of type III collagen.

Adult↗

Experimental dystonia induced by quaternary-chlorpromazine.

When quaternary-chlorpromazine (Q-CPZ) was administered intraventricularly (ICV) to rats, it induced a lateralized dystonic reaction, which progressed to head-to-tail barrel rolling. The syndrome persisted for approximately 10 minutes, was not antagonized by pretreatment with drugs used to treat extrapyramidal movement disorders, and could not be mimicked by ICV administration of dopamine antagonists. Unlike known dopamine antagonists, Q-CPZ does not alter dopamine turnover, cause prolactin release in vivo, or bind to dopamine/neuroleptic receptors in vitro. These data suggest that Q-CPZ differs substantially from CPZ in pharmacologic action, and that it elicits a behavioral syndrome of potential use for studying dystonias.

3,4-Dihydroxyphenylacetic Acid↗

Lung carcinoma associated with bullous lung disease in young men.

Over a 6 year period, three cases of pulmonary carcinoma in young men with severe bullous lung disease were seen at Washington University Medical Center. The patients did not have a long cigarette-smoking exposure. It would seem that patients with severe bullous lung disease are at a higher risk for the development of pulmonary neoplasm than the general population. Physicians should be aware of this association to expedite diagnosis and therapy.

Adult↗

Relationship of prostaglandin secretion by rabbit alveolar macrophages to phagocytosis and lysosomal enzyme release.

The phospholipids of rabbit alveolar macrophages were pulse-labelled with [(14)C]-arachidonic acid, and the subsequent release of labelled prostaglandins was measured. Resting macrophages released measurable amounts of arachidonic acid, the prostaglandins E(2), D(2) and F(2alpha) and 6-oxoprostaglandin F(1alpha). Phagocytosis of zymosan increased the release of arachidonic acid and prostaglandins to 2.5 times the control value. In contrast, phagocytosis of inert latex particles had no effect on prostaglandin release. Indomethacin inhibited the release of prostaglandin, and, at high doses (20mug/ml), increased arachidonic acid release. Analysis of the cellular lipids showed that after zymosan stimulation the proportion of label was decreased in phosphatidylcholine, but not in other phospholipids or neutral lipids. Cytochalasin B, at a dose of 2mug/ml, inhibited the phagocytosis induced by zymosan but increased prostaglandin synthesis to 3.4 times the control. These data suggest that the stimulation of prostaglandin synthesis by zymosan is not dependent on phagocytosis. Exposure to zymosan also resulted in the release of the lysosomal enzyme, acid phosphatase. Furthermore, cytochalasin B augmented the zymosan-stimulated release of acid phosphatase at the same dose that stimulated prostaglandin synthesis. However, indomethacin, at a dose that completely inhibited prostaglandin synthesis, failed to block the lysosomal enzyme release. Thus despite some parallels between the release of prostaglandins and lysosomal enzymes, endogenous prostaglandins do not appear to mediate the release of lysosomal enzymes. The prostaglandins released from the macrophages may function as humoral substances affecting other cells.

Acid Phosphatase↗

Atypical antidopaminergic properties of CI-686: a potential antipsychotic agent.

The effects of the antipsychotic/antidepressant drug CI-686 on apomorphine- and amphetamine-induced stereotypies, dopamine metabolism, neuroleptic binding, and serum prolactin levels were determined. CI-686 displayed profiles of activity in each of these systems that differs markedly from those of other antipsychotics. CI-686's unique preclinical profile suggests a mechanism of action other than dopamine antagonism which could have implications regarding current thinking on the pathophysiology of schizophrenia.

Amphetamine↗

Cell cultures derived from embryos and melanoma of poeciliid fish.

In poeciliid fish, melanoma of different degrees of malignancy can be produced by crossing specific genotypes. For a detailed investigation of the processes leading to proliferation or differentiation of the melanoma cells, it is necessary to establish cell cultures. The aim of the present study was to find out the optimal conditions for initiating and culturing poeciliid fish cells for the purpose of establishing cell cultures of melanoma. The optimal method was developed by using small pieces of late embryos as starting material and includes: (a) dispersion of tissue by mild stepwise treatment with a trypsin-EDTA mixture at low temperature; (b) culture of cells in the complex medium 199; (c) supplementation of medium with high percentage (20%) of fetal bovine serum; and (d) stabilization of pH by buffering the medium with HEPES. Under these conditions, primary and secondary cultures of embryonic cells have been initiated. An epithelial-like cell line has been subcultured for more than 80 passages. The method developed for embryonic tissues was used to start cell cultures from melanoma of platyfish-swordtail hybrids. Until now, only cells of rapidly growing malignant albino melanoma could be maintained in primary cultures. Secondary cultures could not be initiated since the melanoma cells tended to differentiate and stopped growing before a confluent monolayer was formed.

Animals↗

Receptor-mediated binding and internalization of leukocyte elastase by alveolar macrophages in vitro.

Radioiodinated leukocyte elastase was found to bind rapidly and specifically to alveolar macrophages in vitro. In contrast to the binding of pancreatic and bacterial proteases, leukocyte elastase binding did not require the presence of alpha 2 macroglobulin. The binding was inhibited by an excess of unlabeled enzyme and was saturable by increasing elastase concentrations. Leukocyte elastase binding thus met criteria for receptor-mediated binding, with and estimated association constant of 4.97 x 10(5) M-1 and an estimated total of 640 x 10(6) binding sites/cell. It differed from the previously described binding of lysosomal glycosidases to macrophages in that it was insensitive to trypsin pretreatment, did not require calcium ions, and was not inhibited by yeast mannan. High-resolution autoradiography indicated that the cell-associated radiolabeled leukocyte elastase was rapidly incorporated into phagolysosomes. Macrophage binding may have a role in clearance of leukocyte elastase from tissue sites where alpha 2 macroglobulin is absent or present in low concentration. Thus, enzyme uptake by alveolar macrophages may be an important factor in the amelioration of lung tissue injury by extracellular leukocyte elastase.

Autoradiography↗

The structure of the tips of mammalian respiratory cilia.

The ciliary crown and the relationship of the ciliary crown to the underlying axoneme were studied by electron microscopy in cilia from hamster and rat trachea and bronchioles, and rabbit trachea. The ciliary crown is a cluster of 4 to 6 fibrils 35 nm long protruding beyond the plasma membrane at the tips of the cilia. The fibrils are well preserved after tannic acid-glutaraldehyde-osmium tetroxide fixation and have high contrast with a periodic density of 4.5 nm. They stain relatively weakly with phosphotungstic acid. The surface of the fibrils stains with ruthenium red. The microtubules of the axonemem end in a plate of electron dense amorphous material. A five layered disc occupies the space between the membrane and the amorphous plate at the tip of the axoneme. The plasma membrane can be dissolved with the detergent triton X-100 without loss of the ciliary crown. This indicates that the ciliary crown is composed of transmembranous filaments which are bound to the disc at the tip of the axoneme.

Animals↗

Peritoneal exudate cells. V. Influence of age, sex, strain and species on the induction and the growth of macrophage colony forming cells.

We investigated the effects of age, sex and strain in the induction of peritoneal exudate colony-forming cells (PE-CFC) in mice. Sex and age (ranging from 3 weeks to 12 months) had no significant effect on the induction of PE-CFC. However, we found significant difference between strains in terms of the number of nucleated cells and the proportion of PE-CFC in exudate cells. When we investigated the mechanisms behind this strain difference, we found that it was due to neither the type of colony-stimulating factor employed in culture, nor the type of stimulants used to induce the exudate, nor the difference in the kinetics of appearance of PE-CFC in the peritoneal cavity. We also studied the induction of PE-CFC in rats and hamsters and the growth of these cells in vitro. Unlike mouse cells, PE-CFC from rats and hamsters could also use media conditioned by cells from other species as a source of colony-stimulating factor.

Age Factors↗

Evolution of a genetic code simulated with the computer.

A simple selforganizing model system of molecules is considered and it is demonstrated by a computer simulation, that a genetic code of 16 elements (aminoacids) can gradually be formed by such a system in the course of many generations. By a number of rare chance events, each suppressing other events of equal a priori probability, a single code results out of an immense number of possible codes of the same a priori probability. The result is discussed in relation to the uniqueness of the genetic code in living systems. The computer simulation emphasizes a particular step in a model pathway discussed elsewhere consisting of many assumed physicochemical steps leading to a genetic apparatus.

Base Sequence↗

Elastase secretion by peritoneal exudative and alveolar macrophages.

Mouse alveolar macrophages (AM) cultured in the absence of serum secrete an elastolytic enzyme. The elastase from AM resembles the previously described elastase from peritoneal macrophages (PM) in pH optimum and inhibition profile. The macrophage enzymes do not appear to be stored, and with periodic changes in the culture medium, accumulate extracellularly for up to 10 days. Resident PM produce barely detectable levels of extracellular elastase unless given a phagocytic load. Thioglycollate-stimulated peritoneal exudative macrophages (PEM), however, secret easily detectable levels of elastase, which can be further increased with a phagocytic load. Without any additional stimulation, AM secret an elastolytic activity comparable to that of the PEM receiving a phagocytic load, but unlike PM they do not increase elastase secretion after phagocytosis.

Animals↗

The induction of pulmonary emphysema with human leukocyte elastase.

Purified human leukocyte elastase was injected into the tracheas of 46 hamsters. Thirteen animals died spontaneously within 1 week, with extensive lung hemorrhage. The elastin content of the lungs was only slightly less than control values 3 hours after injection. At 2 months, the lungs of the remaining animals showed mild, patchy emphysema and morphometric changes consistent with emphysema. These results contrasted with the effects of a similar elastolytic dose of pancreatic elastase administered to 26 other hamsters in that only one animal died spontaneously, the lung elastin content 3 hours after injection was substantially decreased, and severe emphysema was present 2 months later. Leukocyte elastase appears to be capable of causing emphysema; but unlike pancreatic elastase, leukocyte elastase produces emphysema that is mild, even at a dose sufficient to produce intense lung hemorrhage and a high mortality.

Animals↗

Desquamative interstitial pneumonia-like reaction accompanying pulmonary lesions.

Six patients with specific pulmonary diseases had pulmonary tissue surgically resected for diagnostic purposes. All six cases were characterized by space-occupying lesions surrounded by a peculiar reaction of the pulmonary parenchyma indistinguishable from desquamative interstitial pneumonia. If small biopsies from these areas had been taken, a diagnosis of desquamative interstitial pneumonia would have been made, and the underlying process would have gone undetected. These cases corroborate even further the concept that desquamative interstitial pneumonia is a pattern of pulmonary reaction, rather than a well-defined disease entity. Furthermore, it seems advisable to make the dianosis of desquamative interstitial pneumonia only when other conditions have been carefully ruled out by thorough clinical and pathologic investigations.

Adult↗