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Biomedical subjects

S Keller

Publications and source records attributed to S Keller.

At least 109 records · Page 6Linked to original sources

Cigarette smoke impairs elastin resynthesis in lungs of hamsters with elastase-induced emphysema.

The severity of pulmonary emphysema can be affected by exposure to cigarette smoke in several ways. Inactivation of alpha-1-antitrypsin and recruitment of leukocytes to lung airways shifts the protease-antiprotease balance towards increased elastolytic activity. The present study demonstrates an additional effect of cigarette smoke inhalation and retardation of the repair process and of the neosynthesis of cross-linked elastin. Hamsters with elastase-induced emphysema, exposed to cigarette smoke for 1 wk immediately after elastase administration, showed a 40% reduction of 14C-lysine incorporation into the elastin-specific cross-links, desmosine, and isodesmosine. Concomitantly, there was a decrease in the level of lung lysyl oxidase to that observed in uninjured control animals, in sharp contrast to the sevenfold increase in lysyl oxidase activity in hamsters with elastase-induced emphysema recovering under atmospheric conditions. These findings suggest that impairment of the production of lysyl oxidase and the resynthesis of cross-linked elastin by smoke inhalation exacerbates alveolar destruction.

Animals↗

Spontaneous spinal cord "injury potential" in the rat.

A marked ionic change in both the intra- and the extracellular space at the site of an acute spinal cord lesion has been reported in the literature. The present study was undertaken to measure spontaneous electrical potentials that might be associated with the previously observed ionic shifts. With the use of an impact (weight drop) model of cord injury in rats, lesions were induced at T-8. DC potentials were measured simultaneously both rostrally and caudally with respect to site of injury over a time course of 4 hours after injury. The potentials were positive with respect to lesion site, and the intensity decreased with time during 4 hours of observation. These results seem to support reported ionic shifts and migrations in injured cords and represent, to our knowledge, the first reported measurement of spontaneous injury potential in the cord of a mammal.

Animals↗

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↗

Physical fitness level and autonomic reactivity to psychosocial stress.

Two studies explored the influence of aerobic fitness level on autonomic reactivity to psychosocial stress. Experiment 1 employed a correlational, repeated measures design. A total of 45 men who were physically trained, untrained, or training were tested at three-week intervals over nine weeks. The measure of autonomic reactivity was lability in electrodermal activity during two speeded mental tasks designed to induce psychosocial stress. In the initial test session, trained subjects showed faster autonomic recovery from this stress than did untrained or training subjects; in subsequent test sessions involving the repeated administration of the same tasks, the three groups were indistinguishable. Experiment 2 employed 60 subjects who were randomly assigned to 10-week aerobic exercise, meditation, or music appreciation programs. In each session, two psychosocial stressors selected from a battery of six tasks were counterbalanced across treatments and sessions. Over the course of the study, participants in the exercise program improved significantly in physical fitness and also showed faster recovery in the electrodermal response. This quicker autonomic recovery may allow the aerobically fit to cope more effectively with emotional stress.

Adolescent↗

Quantitative studies of argyrophilic APUD cells in airways. III. The effects of sensitization and anaphylactic shock.

A morphometric study of argyrophilic APUD cells in airways and intestine of guinea pigs during sensitization with ovalbumin and anaphylactic shock is reported. The APUD cell densities are expressed as APUD cell number/mm of airway or gut perimeter length and as APUD cell/100 epithelial cells. The latter ratio is useful to distinguish specific changes in APUD cells from generalized epithelial changes. Control guinea pigs have greater densities of APUD cells in the larynx (0.075 +/- 0.021 APUD/100 nuclei) than in more distal airways: trachea (0.025 +/- 0.007), bronchi (0.013 +/- 0.003), and bronchioles (0.003 +/- 0.002). In the ileal mucosa APUD cells are present in greatest density: 10.0 +/- 3.0 APUD/100 nuclei. Immunization with ovalbumin followed by sham challenge with saline results in 2- to 10-fold increases in APUD cell densities in all airway sectors as compared to control subjects. These differences are statistically significant in the trachea and bronchioles when ratios of APUD cells/mm are compared to control subjects but only in bronchioles when the ratios of APUD cells/100 nuclei are calculated. Immunization with ovalbumin followed by challenge with this antigen results in similar changes in large airways. However, bronchiolar APUD cells exhibit a 30-fold decrease in density when compared to immunized-sham challenged animals within the limits of our ability to quantitate them. Our findings suggest that argyrophilic APUD cells participate in the complex physiologic events that take place in the lung during sensitization and anaphylaxis.

APUD Cells↗

Measurement of cross-linked elastin synthesis in bleomycin-induced pulmonary fibrosis using a highly sensitive assay for desmosine and isodesmosine.

Cross-linked elastin synthesis was measured in the intratracheal bleomycin model of interstitial pulmonary fibrosis by incorporation of 14C-lysine into the elastin-specific crosslinks, desmosine and isodesmosine. Detection of the labeled crosslinks was facilitated by development of a highly sensitive assay utilizing thin-layer electrophoresis. The results indicate that crosslinked elastin synthesis is significantly elevated from controls (p less than 0.05) at 1 to 3 weeks after exposure to bleomycin and returns to normal by 5 weeks. The increases in labeled elastin synthesis are not directly related to changes in either total lung protein synthesis or the pool size of the 14C-lysine. In comparison with collagen and glycosaminoglycan synthesis in this model of lung injury, maximal increases in cross-linked elastin formation occur later, but overlap with the elevated synthesis of these other connective tissue components. The marked increase from normal in cross-linked elastin synthesis in this model suggests that this tissue component is an important part of the fibrotic response of the pulmonary parenchyma and may play a role in the observed alterations in lung structure and function.

Amino Acids↗

The content of elastin in the uterine cervix.

Mature, crosslinked elastin has been isolated from 4 human and 12 monkey uterine cervices. A modification of previous methods for determination of elastin content was devised to quantitate the low amounts of elastin in the crude connective tissue of uterine cervices. The percentage of elastin was found to range between 0.9 and 2.4% and did not appear to change at various stages of gestation.

Amino Acids↗

An aetiological evaluation of increased occurrence of congenital limb reduction abnormalities in Hungary, 1975-1978.

In Hungary a significant increase occurred in the birth prevalence of congenital limb reduction abnormalities from 1975 to 1978 after the introduction of a new population policy in 1974. A case-control study showed a slight increased use of drugs for ovulation induction, oral contraceptives prior to conception and more frequent extramarital births as well as unwanted pregnancies.

Abnormalities, Drug-Induced↗

A simple procedure for the isolation of pulmonary parenchyma free of major blood vessels and airways for biochemical studies.

A new method of preparation of lung parenchyma free from small and medium sized airways and blood vessels is described. The lung is frozen in the inflated state and cut into thin slices to facilitate visualization and separation of large blood vessels and airways. With the aid of a special steel brush mounted on a kitchen blender most of the smaller as well as medium sized blood vessels and airways are easily shaved off and subsequently separated from the parenchyma by sieving through a 20-mesh sieve. The fall-through portion consists almost entirely of alveoli. Amino acid analysis of elastin separated from the sieved fragments is similar to lung parenchymal elastin isolated and dissected from fresh lung tissue.

Animals↗

Separation of elastin components by thin layer chromatography and electrophoresis.

Several methods are described which employ thin layer chromatography and electrophoresis for investigations into the structure and synthesis of crosslinked elastin. These procedures are more sensitive and involve less elaborate equipment than separation on paper. The methods described include an electrophoretic procedure for detecting the cross-linking amino acids in elastin hydrolysates, a method for completely separating desmosine, isodesmosine and merodesmosine in these hydrolysates, and a method for producing two-dimensional peptide maps of elastase digests of elastin.

Amino Acids↗