Search PubMed⌕ Search

Biomedical subjects

R Breuer

Publications and source records attributed to R Breuer.

At least 91 records · Page 5Linked to original sources
PubMed1988

An 18-month study of the effects on hamster lungs of intratracheally administered human neutrophil elastase.

A study was made of the evolution of emphysema and airway injury induced in the lungs of male golden Syrian hamsters by a single intratracheal injection of 350 micrograms human neutrophil elastase (HNE). Saline control and HNE-treated groups of 8 animals were studied 1, 3, 6, 12, and 18 months posttreatment. HNE treatment caused a significant increase in all lung volumes and a significant decrease in maximum expiratory flows at all study times. The mean linear intercept (MLI) values of the left lung were significantly increased over control values. There was no progression with time in MLI values, lung volumes, or lung compliance. Secretory-cell metaplasia was present at 1 month and persisted throughout the study. The HNE-treated lungs showed clusters of ferric iron-containing macrophages in the terminal airspaces. The amount of iron in the lungs, determined morphometrically, was greatest at 1 month, was decreased by 6 months, and then did not change further to 18 months. At 18 months the amount of iron was still significantly above control amounts. We conclude that the airway and parenchymal lesions induced by HNE persist without progression for 18 months. Clearance of ferric iron, which was probably a result of the hemorrhage induced by HNE treatment, continued for 6 months with no evident subsequent clearance.

Animals↗
PubMed1988

Interstitial pneumonitis in T cell-depleted bone marrow transplantation.

The incidence of interstitial pneumonitis (IP) was reviewed in 80 consecutive patients who received allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) for malignant and non-malignant diseases. Pretransplant conditioning used in malignant disorders included total lymphoid irradiation (TLI) 150 cGy x 4, total body irradiation (TBI) 200 cGy x 6, and cyclophosphamide (CY) 120 mg/kg. In non-malignant diseases conditioning included no TBI, but adjusted doses of TLI in addition to CY (severe aplastic anemia) or CY and busulfan (severe beta-thalassemia major). In the malignant group only one patient developed graft-versus-host disease (GVHD) grade I; IP developed in 12 out of 61 patients (19.7%) and IP-associated fatality occurred in five patients (8.2%). Cytomegalovirus (CMV) was associated with only two of the five fatal IP. In the non-malignant group there was no GVHD; one patient out of 19 (5.2%) had IP, which was fatal and not associated with CMV. These data indicate that fatal IP may appear in the absence of GVHD. The relatively low incidence of IP-related mortality in recipients of allogeneic T lymphocyte-depleted BMT suggests that although prevention of GVHD and elimination of drugs used for GVHD prevention may reduce the incidence of fatal pulmonary complications, other approaches have to be investigated for complete prevention of IP which still represents a major complication in patients with malignant hematologic disorders treated by allogeneic BMT.

Adult↗
PubMed1987

An ultrastructural morphometric analysis of elastase-treated hamster bronchi shows discharge followed by progressive accumulation of secretory granules.

An ultrastructural morphometric analysis of bronchial secretory cells was carried out on hamsters treated intratracheally with 300 micrograms of human neutrophil elastase (HNE) in 0.5 ml saline, saline alone, or left untreated. Five to 6 animals were killed at 2 h and at 3, 8, and 16 days after treatment. Electron micrographs were prepared from the hilar region of the left main intrapulmonary airway; 125 +/- 16 (mean +/- SE) granulated secretory cells extending from basement membrane to lumen were analyzed for each group. The number (Ng) and area (Ag) of granular profiles per cell, the area of cell profiles (Ac), and the volume density of secretory granules per cell (Vv) were determined using an electronic image analyzer. There were significant decreases in Ng, mean Ag, and Vv in the 2-h HNE group when compared with the saline group. Values of Ng, mean Ag, and Vv were similar for HNE and saline groups at 3 days, but were significantly increased at 8 and 16 days. The Ac of HNE-treated groups was similar to their saline control groups at all time points except at 16 days when the HNE-treated group enlarged to double that of its saline control group. An ultrastructural differential cell count showed a decrease in frequency of granulated secretory cells at 2 h and an increase at 8 and 16 days; there was an inverse change in the frequency of nongranulated secretory cells at these times. The proportion of ciliated, preciliated, and indeterminate cells remained constant over time in all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The ultrastructure of hamster bronchial epithelium.

The central intrapulmonary bronchi of adult male Syrian hamsters were examined by electron microscopy to identify the principal types and proportions of epithelial cells. A differential count of cells displaying both a basal lamina and luminal border (transepithelial cells) showed that, on average, ciliated cells constituted 63% and granule-containing (granulated) secretory cells 25% of the total. Other transepithelial cells included nongranulated secretory cells (9%), preciliated cells (1.5%), and indeterminate cells (1%). The most frequent granulated secretory cell (77% of the population) was the Clara cell. It was identified by the presence of prominent apical smooth endoplasmic reticulum and secretory granules. It was subclassified into three types based on the presence or absence of rough endoplasmic reticulum and on granule morphology. Mucous cells (little or no smooth endoplasmic reticulum but with typical mucous granules) constituted approximately 20% of the granulated secretory cells. Serous cells were very infrequent. A differential count of nucleated epithelial cells demonstrated an average of 2% basal cells (hemidesmosomes present) and 20% pseudobasal cells (hemidesmosomes absent). Neuroepithelial bodies and solitary "small-granule" cells were infrequent. Brush cells and apoptotic bodies were rarely found but are noteworthy because their occurrence in hamster airways was not demonstrated previously. These results provide a foundation for subsequent analysis of alterations of epithelial homeostasis induced by injurious agents of exogenous and endogenous origin.

Animals↗
PubMed1987

An ultrastructural study of the response of hamster bronchial epithelium to human neutrophil elastase.

The central intrapulmonary bronchi of hamsters were examined by transmission electron microscopy at varying times following intratracheal instillation of human neutrophil elastase (HNE) or its vehicle, saline. Two hours after HNE treatment, there was a marked irregularity of the surfaces of many nonciliated epithelial cells; a differential count of transepithelial cells (those with both a basal lamina and luminal border) demonstrated a significant decrease in the proportion of granule-containing (granulated) secretory cells and a corresponding increase in nongranulated secretory cells. By 3 days after HNE injection, the differential count had returned to control levels and cell surface alterations were less evident. By 8 days, the proportion of granulated secretory cells had significantly increased, while that of nongranulated secretory cells had decreased. Many Clara cells developed the characteristics of mucous cells so that mucous cells constituted 57% of the secretory cells compared to 14% for the saline controls. The mucous cells contained an increased number of mucous granules including bizarre forms never seen in controls. By day 16, the average mucous cell proportion had increased to 75%; the mucous cells were larger and contained many more secretory granules than at day 8. At no time was there evidence of overt cell injury or alteration of extracellular connective tissue due to HNE. Basal and pseudobasal cells, distinguished by the presence or absence of hemidesmosomes, did not change as a percentage of total nucleated epithelial cells. Saline had no effect on the differential cell count compared to untreated values. Our results indicate a strong likelihood that HNE causes early discharge of secretory granules and alters the phenotypic expression of Clara cells so that they produce abundant, often abnormal mucous granules. The mechanism of HNE-induced disturbance of epithelial homeostasis is unknown, but the early irregularity of nonciliated epithelial cell surfaces may signify an important event in the evolution of the resultant lesion.

Animals↗
PubMed1986

Effect of varying the time interval between intratracheal administration of eglin-c and human neutrophil elastase on prevention of emphysema and secretory cell metaplasia in hamsters. With observations on the fate of eglin-c and the effect of repeated instillations.

Eglin-c is a naturally occurring polypeptide of 70 amino acids with a molecular mass of 8,100 daltons. It is a strong inhibitor of human neutrophil elastase (HNE) and cathepsin-G, and, when given intratracheally to hamsters 1 h before human neutrophil elastase, it can prevent or ameliorate the emphysema produced by HNE. The present experiments were designed to determine the duration of the effectiveness of eglin-c, prepared by DNA technology from Escherichia coli, in preventing the emphysema and secretory cell metaplasia induced by HNE. Eglin-c (2,000 micrograms in 0.5 ml saline) was effective in ameliorating emphysema, as determined histologically and physiologically, when it was given intratracheally to hamsters 1, 2, 4, and 8 h before the intratracheal instillation of 300 micrograms of HNE. Eglin-c ameliorated bronchial secretory cell metaplasia when given 1 h before HNE but not when the time intervals were 2 h or longer. The clearance of [3H]eglin-c from the lungs was assessed. Four h after intratracheal instillation of 446 micrograms of [3H]eglin-c, 33% of the tritium was found in the lung tissue and bronchoalveolar lavage fluid; 83% of the radioactivity in the lavage fluid supernatant was associated with functionally active eglin-c. No evidence of bronchopulmonary toxicity was seen in hamsters given 4 intratracheal instillations of 2,000 micrograms of eglin-c at 1-wk intervals.

Animals↗
PubMed1986

Serine proteases stimulate mucous glycoprotein release from hamster tracheal ring organ culture.

The effects of several neurohumoral agents and serine proteases on glycoconjugate release from hamster tracheal organ cultures were assessed. The beta-adrenergic agonist isoproterenol inhibited glycoconjugate release, and its effect was abolished by the specific beta-blocking agent propranolol. A cholinergic agonist, pilocarpine, marginally increased glycoconjugate release, and its effect was abolished by the antagonist atropine. Human neutrophil elastase and porcine pancreatic trypsin consistently increased glycoconjugate release by 1.8 to 2.8-fold. When the proteases were inactivated, they were no longer effective in stimulating glycoconjugate release. Histologic and electron microscopic analysis of the protease-treated organ cultures revealed no discernible toxic reaction. In addition, organ cultures prelabeled with chromium 51 did not release an increased amount of radioactivity when treated with the proteases. Biochemical analysis of the glycoconjugates released into the culture medium showed them to be of high molecular weight (90% eluted in the void volume of a Sepharose 6B column) and to be resistant to digestion with hyaluronidase and heparinase, properties consistent with mucous glycoproteins. The mechanism of protease-induced glycoconjugate release is unknown. We speculate that stimulation of airway secretory cells by serine proteases of neutrophilic or other inflammatory cell origin may play a role in the increased airway secretion that is characteristic of acute tracheobronchitis.

Animals↗
PubMed1985

Effect of combined human neutrophil cathepsin G and elastase on induction of secretory cell metaplasia and emphysema in hamsters, with in vitro observations on elastolysis by these enzymes.

To determine whether purified human neutrophil cathepsin G (Cat-G) can act by itself or in concert with purified human neutrophil elastase (HNE) in the induction of emphysema and bronchial secretory cell metaplasia (SCM), we gave golden Syrian hamsters 100 micrograms of HNE alone or in combination with either 100 or 200 micrograms of Cat-G. Other groups of animals received intratracheal doses of up to 600 micrograms of Cat-G alone. The severity of emphysema was determined from measurements of lung volumes, compliance, forced expiratory flow, and the mean linear intercept. The severity of SCM in the main airways was graded on sections stained by the alcian blue and periodic acid-Schiff reaction. The Cat-G was a weak inducer of SCM; significant SCM was produced by 400 and 600 micrograms but not by 100 or 200 micrograms or 200 micrograms of Cat-G. The Cat-G (100 and 200 micrograms) did not potentiate the SCM induced by 100 micrograms of HNE. The Cat-G alone did not produce emphysema, and neither 100 nor 200 micrograms of Cat-G potentiated the mild emphysema induced by 100 micrograms of HNE. These results were not consonant with a report that Cat-G and HNE were synergistic in solubilizing human lung elastin. We therefore measured the ability of Cat-G and HNE to solubilize several radiolabeled elastins. The combination of Cat-G and HNE did not solubilize significantly more hamster lung elastin (23%) than the sum of their individual activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Eglin-c, a polypeptide derived from the medicinal leech, prevents human neutrophil elastase-induced emphysema and bronchial secretory cell metaplasia in the hamster.

Eglin-c (Eg-c), a polypeptide with a molecular mass of 8,100 daltons, was purified from the medicinal leech Hirudo medicinalis. The Eg-c was tritiated by reductive methylation for in vitro studies. Incubation of 2.1 X 10(-10) moles of human neutrophil elastase (HNE) with 3H-elastin in the presence of 8.2 X 10(-10) moles of 3H-Eg-c inhibited 98.7% of the elastolytic activity of the enzyme. Using Sephadex G 100 chromatography and 1.7 moles of 3H-Eg-c per mole of HNE, a 34,000-dalton complex (3H-Eg-c-HNE) was observed. The stability of the complex formed between 3H-Eg-c and HNE that had been inactivated with succinyl-ala2-pro-val CH2Cl was much less than that of the 3H-Eg-c-HNE complex. In vivo studies were carried out in weight-matched groups of anesthetized golden Syrian hamsters given 100, 300, 500, or 2,000 micrograms of Eg-c in 0.5 ml saline intratracheally 1 h before 300 micrograms HNE was administered intratracheally. Control animals received saline followed by HNE or 2 doses of saline 1 h apart. Eight weeks later, lung statics and dynamics were measured in anesthetized animals, followed by histologic study of lung parenchyma and the mucosa of the large intrapulmonary airways. There were no deaths, and final mean body weights were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Proteolytic activity of human neutrophil elastase and porcine pancreatic trypsin causes bronchial secretory cell metaplasia in hamsters.

The authors wished to determine whether secretory cell metaplasia (SCM) induced in the bronchi of hamsters by human neutrophil elastase (HNE) was enzymatically mediated. We also wished to determine whether SCM could be induced by a proteolytic enzyme devoid of elastolytic activity. Accordingly, groups of weight-matched hamsters were given a single intratracheal instillation of 0.5 ml of saline solution containing one of the following: 300 micrograms of HNE purified from blood neutrophils, n = 14; 300 micrograms of HNE inactivated with Suc-Ala-Ala-Pro-Val chloromethyl ketone (CMK), n = 10; 500 micrograms of porcine pancreatic trypsin treated with CMK to eliminate residual active elastase, n = 10; 500 micrograms of trypsin inactivated by tosyl lysine chloromethyl ketone, n = 10; 2 micrograms CMK, n = 10; and saline alone, n = 10. Seven untreated animals served as additional controls. Twenty-one days post treatment, 5-6 micron paraffin-embedded sections, from the left lung hilar region, stained by Alcian blue and periodic acid-Schiff reaction were graded on a five-point scale for determination of the secretory cell index, which reflects SCM. Both elastase and trypsin produced severe SCM: mean +/- SEM secretory cell indices were 2.96 +/- 0.11 and 2.72 +/- 0.19, respectively, compared with values of 0.90 +/- 0.35 for the untreated group and 0.93 +/- 0.46 for the saline group (p less than .05). The secretory cell indices of the groups treated with inactivated elastase or trypsin were comparable to those of the saline-treated and untreated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Quantitative study of secretory cell metaplasia induced by human neutrophil elastase in the large bronchi of hamsters.

To explore the time course and the mechanism of development of bronchial secretory cell metaplasia (SCM) induced by human neutrophil elastase (HNE), anesthetized hamsters were injected intratracheally with 300 micrograms highly purified HNE in 0.5 ml saline solution; saline-injected and untreated animals served as controls. At 3, 8, 16, and 21 days after treatment, animals were killed and their lungs fixed by vascular perfusion. Samples from the hilar region of the left lung, containing the main axial airway and its proximal branches, were embedded in Epon-Araldite, and 1 micron sections were stained with methylene blue. Epithelial cells with a luminal border were categorized into three cell types and expressed as a percent of total cells counted (mean 1900 per animal); cells containing at least three mucin granules were classified as secretory, ciliated cells displayed cilia or basal bodies, and cells with none of these characteristics were classified as indeterminate. Percentages of the three cell types in saline-treated animals, at all time points, were comparable to those in the untreated controls. With HNE treatment the secretory cell percentages were higher at 16 days (mean +/- SEM, 36.4% +/- 3.2%) and at 21 days (35.7% +/- 2.9%) than in the untreated animals (18.2% +/- 1.8%, P less than 0.05). The percentage of the indeterminate cells in the HNE group was decreased at days 8, 16, and 21 (7.2% +/- 1.6%, 5.0% +/- 1.4%, and 8.2% +/- 2.5%, respectively) compared with that in the untreated group (21.7% +/- 2.5%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Occult mycetoma.

Explore the source record for details and available documents.

Adult↗
PubMed1981

Inappropriate secretion of antidiuretic hormone and mycoplasma pneumonia infection.

A patient with chronic bronchitis and acute respiratory failure due to mycoplasma pneumonia received excess parenteral fluid and developed hyponatremia associated with generalized seizures. The low serum osmolarity and elevated urine osmolarity were consistent with SIADH. Treatment with erythromycin and water restriction resulted in the complete recovery of her acute respiratory condition and return of the serum sodium and osmolarity values to normal.

Aged↗