Biomedical subjects

A F Tryka

Publications and source records attributed to A F Tryka.

47 records · Page 3Linked to original sources

PubMed1985

Long-term effects of repeated exposure to 3-methylfuran in hamsters and mice.

Male and female Syrian golden hamsters were exposed for 2 h once a week for 10 consecutive weeks to 344 mumol/l of 3-methylfuran (3MF), an agent known to produce acute Clara-cell necrosis. Ten months later their respiratory function was evaluated. No functional differences were found between control and treated animals, and histopathologic evaluation of the lungs did not reveal any major treatment-related alterations. Male and female BALB/c mice were exposed for 1 h to 26.8 mumol/l of 3MF once weekly for 10 wk. After 2 yr the tumor incidence in exposed animals was not increased when compared to controls. It is concluded that the acute Clara-cell necrosis produced by 3MF at the doses used is of little long-term consequence.

Air Pollutants↗

PubMed1985

Short-term regional clearance of an inhaled submicrometric aerosol in pulmonary fibrosis.

Regional clearance of submicrometric aerosol during 5 days was studied in control hamsters and in those with diffuse interstitial pulmonary fibrosis. Fibrosis was induced by treatment with bleomycin (1.6 U/kg) and oxygen (70% for 72 h) 80 days earlier. Diseased and control animals were exposed for 30 min to an insoluble colloidal 198Au aerosol (AMAD, 0.62 micron; sigma g, 1.35). Five diseased and 6 control animals were killed immediately (Day 0); 6 diseased and 6 control animals were killed 5 days later (Day 5). All lungs were excised, dried at TLC, sliced into 1-mm sections, and dissected into pieces. When compared with deposition in Day 0 control lungs, 26.3% of the particles had been cleared 5 days after exposure from the control lungs. Diseased animals cleared 44.6% of the particles (p less than 0.05, compared with Day 0 diseased animals). Examination of regional clearance on the basis of lobar differences, apex to base levels, and presence of airways also reflected increased clearance in the fibrotic animals. The parenchymal distribution of particle retention at Day 0 was less uniform in the fibrotic animals than in the control animals and was not significantly altered after 5 days of clearance in either group. Particle clearance may be greater in diseased lungs because of accelerated alveolar-bronchiolar transport of particles or particle-containing macrophages.

Aerosols↗

PubMed1984

Alterations in alveolar macrophages in hamsters developing pulmonary fibrosis.

Hamsters treated with intratracheally instilled bleomycin (0.16 U/100 g) followed by a 72-hr exposure to 70% oxygen develop a slowly progressive interstitial pneumonitis with fibrosis. Lung lavage was performed during fibrogenesis at 30, 60, and 120 days after treatment. The number of macrophages recovered was increased at all of these times. Macrophages were evaluated using flow cytometry and a monoclonal antibody specific for a surface antigen present on mature lung macrophages but deficient in younger cells. The mean density of antigenic sites per cell surface area was significantly lower than control values at the three times studied (-24.7, -20.0, and -20.9%). Thus, a significant fraction of macrophages present in this model of progressive pulmonary fibrosis are immature. The in vivo uptake of radioactive colloidal gold by the pulmonary macrophages was also determined. Thirty days after treatment, macrophage endocytosis of colloidal gold was reduced by 22% of control. The total number of harvested macrophages increased twofold, however, a change that usually increases endocytotic rates. It is concluded that macrophages are increased during fibrogenesis and that this increase is caused by a continued influx of new macrophages. In addition, the phagocytic function of these macrophages is less efficient.

Animals↗

PubMed1984

Differences in effects of immediate and delayed hyperoxia exposure on bleomycin-induced pulmonary injury.

Several reports have suggested that patients treated with bleomycin may be at greater risk of developing respiratory failure when exposed to elevated concentrations of oxygen. We studied the interactions of bleomycin and hyperoxia in Syrian golden hamsters. Animals were instilled intratracheally with bleomycin at a dose of 0.5 unit/100 g of body weight, followed immediately by exposure to 70% oxygen for 72 hours. Mortality was 90% in these hamsters, compared to 15% in an age-matched control group treated with bleomycin alone. Postmortem studies revealed that pathologic changes were confined to the lungs which showed severe, hemorrhagic, diffuse alveolar damage. To determine the effect of delaying exposure to hyperoxia, bleomycin at a dose of 0.5 unit/100 g of body weight was instilled and animals were kept in room air for 1 and 2 months before exposure to 70% or 100% oxygen for 72 hours. No significant increase in mortality or interstitial pneumonitis and fibrosis was seen in these groups during or after the hyperoxic exposures. Mortality in controls treated with saline and hyperoxia was zero. We conclude that simultaneous treatment with bleomycin and hyperoxia results in a synergistic effect on mortality and on the development of pulmonary fibrosis. However, there is no synergism if the hyperoxic exposure is delayed for at least 1 month following bleomycin treatment.

Animals↗

PubMed1983

Retention of inhaled particles in hamsters with pulmonary fibrosis.

Aerosol retention was studied in hamsters 30, 60, and 90 days after the initiation of interstitial pulmonary fibrosis by a combination of bleomycin (bleo), 0.16 U/100 g body weight given intratracheally, and O2, for 72 h. Groups of bleo-O2-treated and control animals were exposed (awake) for 25 min to a 99mTc-labeled insoluble aerosol (activity median aerodynamic diameter, 0.45 micron; geometric standard deviation, 1.3). Within 5 min after exposure, the hamsters were killed and their lungs were excised and dried at total lung capacity, and sliced into 1-mm sections. Slices were dissected into pieces, and an evenness index (EI) was calculated for each piece (formula: see text). With uniformity of retention, all Els would be 1. The distribution of Els in control animals had a mean of 1.0 and a SD of 0.27; 0% of the Els were less than or equal to 0.20. Total retention diminished and was less uniform in bleo-O2-treated animals. At 30 days, the SD increased to 0.62, and 6% of the Els were less than or equal to 0.20. At 60 and 90 days, nonuniformity decreased but was still greater than that in the control animals (SD60 = 0.42, SD90 = 0.36). When examined histologically, individual pieces with low Els had more disease than those with high Els. Local decreases in compliance caused by fibrosis may have altered regional ventilation and retention. Our data also correlate with the progression of fibrosis from a focal lesion at 30 days to a more diffuse lesion at 90 days.

Aerosols↗

PubMed1983

Progressive pulmonary fibrosis in hamsters.

The concomitant treatment of hamsters with bleomycin and hyperoxia results in a synergistic development of pulmonary injury. We exposed hamsters for 72 hr to 70% oxygen following a single intratracheal instillation of bleomycin (0.16 U/100 g body weight). Groups of 10 animals were killed at 3, 6, 10, 30, 60, 90, and 120 days after instillation for histopathologic and morphometric assessment. Diffuse alveolar damage developed acutely. At 30 days, the intense acute cellular infiltrate had subsided, leaving a focal interstitial pneumonitis. Morphometric quantitation at 10 days revealed that 33.5 +/- 5.3% (x +/- SE) of the lung was diseased; there was apparent healing by 30 days, when 10.5 +/- 2.0% of the lung was diseased. However, progression to diffuse pneumonitis with fibrosis was seen at 60, 90, and 120 days, when 30.2 +/- 4.9%, 38.5 +/- 5.8%, and 38.8 +/- 4.5% of the lung was diseased, respectively. In vivo pulmonary function studies on treated animals at 25 and 55 days showed decreasing dynamic compliance and increased minute ventilation, which corroborates the presence of interstitial fibrosis. We conclude that simultaneous treatment of hamsters with bleomycin and hyperoxia results in interstitial fibrosis with a distribution and progression that mimics human pulmonary fibrosis. This model appears ideally suited for the study of progressive fibrosis and will be useful when development of a widely distributed lesion is crucial.

Animals↗

PubMed1982

Leukemic cell lysis pneumonopathy. A complication of treated myeloblastic leukemia.

The course of acute noninfectious pulmonary infiltrates in five patients with myeloblastic leukemia was evaluated. All had circulating blast cells (range, 245-192,000/mm3) and recently had received chemotherapeutic drugs for their leukemia. Within four days of the nadir of their leukocyte counts, a patchy, often multilobar pneumonitis developed. Cultures for bacteria, fungi, and viruses were all negative, and no clinical response was observed to broad-spectrum antibiotics. On lung biopsy, pathologic changes were characterized by diffuse alveolar damage with degenerating blast cells in the interstitium and in organizing alveolar exudates. No potential pathogenic organisms were seen on light or electron microscopy of the biopsy samples. In each case the pulmonary infiltrate resolved without specific therapy. We postulate that lysis of leukemic cells, with subsequent release of their enzyme contents, led to the diffuse alveolar damage observed pathologically. Leukemic cell lysis pneumonopathy may be one of the potential causes of pulmonary infiltrates in leukemic patients and can be distinguished pathologically by its distinctive pattern.

Adult↗

PubMed1982

Potentiation of bleomycin-induced lung injury by exposure to 70% oxygen. Morphologic assessment.

The effects of a single intratracheal instillation of bleomycin followed by exposure to 70% oxygen for 72 h were studied in hamsters. Mortality increased markedly among hamsters exposed to 70% oxygen for 72 h after bleomycin instillation, compared with animals receiving bleomycin and breathing room air. The lethal dose required to kill 50% of the hamsters at 30 days (LD50, 30 day) for bleomycin alone was 0.73 U/100 g body weight, whereas the LD50, 30 day for bleomycin followed by 70% oxygen fell to 0.23 U/100 g body weight. Using morphometry and light microscopy, we found that the amount of diseased lung increased in hamsters given bleomycin with hyperoxia compared with that in those treated with bleomycin alone. After 0.20 U bleomycin and air, 2.8 +/- 1.6% of the lung was abnormal, but with 0.20 U bleomycin followed by 70% oxygen, 42.7 +/- 17.9% of the lung was abnormal. At bleomycin doses that produced no apparent lesions, the addition of 70% oxygen for 72 h produced focal interstitial fibrosis at 30 days. Neither mortality nor significant histologic changes were seen in hamsters treated with saline followed by exposure to 70% oxygen for 72 h. This study demonstrates that hyperoxia potentiates bleomycin damage and suggests that the use of elevated oxygen concentrations in patients being treated with bleomycin should be minimized.

Air↗

PubMed1981

The effect of low-dose aspirin and dipyridamole upon atherosclerosis in the rabbit.

To examine the effect of antiplatelet therapy upon atherosclerosis in an animal model, aspirin and dipyridamole were administered to female New Zealand rabbits while they were fed a 2% cholesterol diet. Four experimental groups of 15 animals were established: Group I (Control), no medication; Group II, aspirin, 40 mg orally five days a week; Group III, dipyridamole, 25 mg orally five days a week; Group IV, aspirin and dipyridamole. After seven weeks, the animals were sacrificed and their aortas were removed and stained. Group means of the percentage of total aortic lumenal surface occupied by gross atheromata were calculated and statistically compared with the control group mean: Group I - 49%, Group II 36%, p = NS, Group III - 47%, Group IV - 25%, p less than .01. Histologic sections of each aorta confirmed the stained areas to be atheromata of varying complexity. The lesions in animals treated with dipyridamole alone exhibited a distinct increase in smooth muscle cell proliferation. For animals receiving a combination of aspirin and dipyridamole the lesions were smaller and less advanced than those in the control group. These findings indicate that experimental atherosclerosis in rabbits is modified by the administration of anti-platelet agents and that atheroma formation is significantly inhibited when aspirin and dipyridamole are given in combination.

Animals↗

PubMed1979

Histopathology in the evaluation of total pancreatectomy for ductal carcinoma.

Whipple resections for pancreatic head carcinoma are often inadequate because tumor is left behind in the body and tail. Thirty-six patients have undergone total pancreatectomy for various conditions, of which 25 have undergone total pancreatectomy, for ductal carcinoma. Thirty-seven per cent of these 25 patients have shown histologic evidence that a Whipple resection would not have adequately removed tumor-bearing pancreatic tissue. Three patients had carcinoma spreading up and along the common bile duct from a primary ductal carcinoma in the head of the pancreas. Four patients had tumor infiltrating in continuity into the pancreatic body and tail at a distance from the palpable tumore in the head well to the left of a Whipple transection site. Five patients had widespread multifocal autonomous tumor involving other areas in the gland but with tumor palpable only in the head of the pancreas. Three patients (12%) died postoperatively. The two year survival rate is 32%, and the five year survival, 19%. Histological factors affecting the survival prognosis include 1) positive nodes, 2) tumor extension up the common duct, and 3) intrapancreatic extension and multicentricity of tumor mandating total pancreatectomy for hope of cure in at least 38% of cases.

Humans↗

PubMedDate not supplied

Absence of lamellar bodies with accumulation of dense bodies characterizes a novel form of congenital surfactant defect.

Two female sibling full-term newborns developed respiratory distress shortly after birth, which progressed to respiratory failure. Tracheal lavage demonstrated presence of surfactant protein A (SP-A), but little surfactant protein B (SP-B), without aberrant surfactant protein C (SP-C). On a lung biopsy performed in both infants, prominent type II pneumocyte hyperplasia was evident. Through ultrastructural examination an absence of normally formed lamellar bodies was determined, with numerous irregular electron dense bodies within the type II pneumocytes. These electron dense bodies could also be identified in the alveolar spaces and alveolar macrophages. No alveolar tubular myelin was present. Abnormally high immunoreactivity for surfactant proteins SP-A, proSP-B, SP-B, and proSP-C was demonstrated by light microscopy. Presence of incompletely processed immunopositive proSP-B, but not proSP-C was observed in the alveolar lumina. No mutations in either the SP-B or SP-C gene were identified by sequence analysis of amplified cDNA. We conclude that these siblings exhibit an inherited surfactant deficiency characterized by abnormal accumulations of surfactant proteins within the pneumocytes. This abnormal accumulation may be due to a primary secretory defect, a defect in surfactant phospholipids, or an abnormal interaction between the phospholipids and surfactant proteins.

Bronchoalveolar Lavage Fluid↗