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Biomedical subjects

W G Johanson

Publications and source records attributed to W G Johanson.

At least 19 recordsLinked to original sources

Association of respiratory tract colonization with adherence of gram-negative bacilli to epithelial cells.

Factors that promote oropharyngeal colonization of seriously ill patients with gram-negative bacilli are as yet poorly understood. In this investigation, 34 subjects who required intensive care were studied; 18 (53%) were colonized with gram-negative bacilli. Oropharyngeal epithelial cells of all colonized patients contained adherent bacilli. Fewer alpha-hemolytic streptococci but greater numbers of Pseudomonas aeruginosa and Klebsiella pneumoniae (P less than or equal to 0.01) adhered in vitro to buccal epithelial cells from colonized patients than to cells from noncolonized patients. Adherence of bacilli to buccal cells was inhibited in vitro by concanavalin A but not by bovine serum albumin or phytohemagglutinin. Brief exposure of buccal cells to trypsin increased adherence of bacilli. Prior adherence of one species of bacilli inhibited subsequent adherence of a second species. These findings suggested that epithelial cells of the upper respiratory tract contain binding sites for gram-negative bacilli. Factors associated with serious illness appear to increase the availability of these binding sites, thus facilitating colonization of the upper respiratory tract with gram-negative bacilli.

Binding Sites

Lung elasticity in regional and diffuse pulmonary fibrosis.

Static deflation air and saline pressure-volume (PV) curves were performed on five normal excised baboon lungs, four with radiation-induced upper lobe fibrosis, and two with diffuse bleomycin-induced fibrosis. Curves were compared visually and using half-inflation pressures (h). When plotted as percent of observed vital capacity vs. transpulmonary pressure, the radiation-associated curves were similar in shape to control curves. Also, h values were not significantly different between the two groups. The bleomycin-associated curves, however, were shifted rightward and exhibited increased h values. PV curves were correlated with connective tissue data. Elastin concentration was increased in the irradiated upper lobes through loss of associated constituents. Elastin accumulated in the lower lobes of the irradiated animals through compensatory growth and in the bleomycin-associated lungs through excessive production. Collagen followed a similar but less dramatic trend. We conclude connective tissue accumulation may not lead to rightward shifted PV curves if accumulation is present in relatively noninflatable lung units, or as part of compensatory lung growth.

Animals

A rat model of chronic respiratory infection with Pseudomonas aeruginosa.

Chronic, nonlethal, pulmonary infection of rats by Pseudomonas aeruginosa can be initiated by intratracheal inoculation of 10(4) bacteria enmeshed in agar beads. The number of bacteria recoverable from the lung increased to approximately 10(6) within 3 days and remained at that number during 35 days of observation. Histologic examination of the infected lungs revealed lesions resembling those seen in lung tissue of humans with acute or chronic nonbacteremic, Pseudomonas aeruginosa pneumonia, including the presence of goblet-cell hyperplasia, focal areas of necrosis, and acute and chronic inflammatory infiltrate. This model should be useful for investigating the interactions between microbial virulence factors and host defense mechanisms.

Animals

Lung bacterial clearance following pulmonary contusion.

Bacterial infections frequently,complicate pulmonary contusion and are the leading cause of death in such patients. This study evaluated the effects of pulmonary contusion alone and contusion associated with other factors on the ability to clear aerosolized bacteria from the lung. Lung bacterial clearance of Staphylococcus aureus and Klebsiella pneumoniae was studied in animals with isolated pulmonary contusion, or contusion associated with blood loss, rapid crystalloid infusion, or steroid administration. An isolated pulmonary contusion produced no impairment of the ability of the contused lung to clear either gram-negative or gram-positive organisms. The addition of acute blood loss and crystalloid infusion resulted in decreased clearance from the contused lung; steroid administration caused a marked depression in lung bacterial clearance from the noninjured lung as well. The canine model described allowed for study of regional differences in bacterial clearance. The data presented support several conclusions; (1) the contused lung is not more susceptible to bacterial infection than the normal lung: (2) acute blood loss renders the contused lung less able to clear bacteria; (3) crystalloid infusion markedly depresses lung bacterial clearance; and (4) steroids have a deleterious antibacterial effect on both contused and noncontused lungs.

Aerosols

Total lung capacity of baboons and humans determined by planimetry of radiographs.

Total lung capacity and radiographic lung area of 25 young and 7 aged baboons (Papio cynocephalus) and seven nonsmoking young adult men were measured. For all subjects, total lung capacity and radiographic lung area raised to the 3/2 power were shown to be highly correlated (r = 0.995). The regression equation for this relationship was total lung capacity (ml) = 78 + 0.234 x radiographic lung area (1.5) (cm2). A more useful regression equation for predicting values of total lung capacity was found to be log total lung capacity = -0.3819 + 1.4153 x log radiographic lung area (r = 0.993), because the standard error of estimate remains a constant percentage of Y values (+/- 12%). Total lung capacity and radiographic lung area were also highly correlated with height, weight and arm span of young baboons and men (r greater than 0.92), but the lungs of aged baboons were disproportionately larger.

Adult

Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons.

Pulmonary fibrosis was induced in eight baboons with bleomycin; five untreated animals were controls. After 45-65 U/kg of bleomycin, lung volumes and diffusing capacity were reduced, and static lung pressure-volume curves were shifted to the right. Right middle lobes were resected at this time in five bleomycin-treated and two control animals. Compared to controls, right middle lobes from bleomycintreated animals had increased weight and contained increased amounts of total protein, collagen, elastin, and DNA; synthesis of collagen and noncollagen protein were also elevated. Occasional alveolar septae were edematous and infiltrated by mononuclear inflammatory cells; a slight increase in collagen was demonstrable histologically. Four of six treated animals died with extensive diffuse interstitial fibrosis after 95 U/kg of bleomycin. Biochemical analyses revealed significantly elevated lobar contents of dry weight, protein, elastin, and collagen. Two animals survived 95 U/kg of bleomycin and were terminated 6 mo after treatment. In these animals, physiologic studies were indicative of restrictive lung disease, but lung histology was nearly normal. Lung weight, total protein, and DNA had returned to control values, but collagen and elastin were increased in amount and concentration. Bleomycin induces an intense inflammatory response in the lung. During this inflammation, connective tissue proliferation occurs in concert with proliferation of other tissue components. Cessation of bleomycin treatment is followed by resolution of inflammation manifested by decreases in tissue mass, cellular content, and nonconnective tissue protein. Collagen and elastin deposited during inflammation are less successfully removed during resolution, leading to a stage characterized by increased concentrations of these proteins. A similar sequence of tissue alterations may occur in idiopathic diffuse interstitial fibrosis of man in response to various lung injuries.

Animals

Lung bacterial clearance in murine pneumococcal pneumonia.

We studied the bactericidal capacity of the rat lung during the development of pneumococcal pneumonia. Pneumonia was produced in a lower lobe by the intrabronchial instillation of 10(4)Streptococcus pneumoniae cells in buffer. Lung bacterial counts progressively increased, reaching 10(7) per lung within 48 h, and the increase was associated with localized atelectasis and consolidation. Bacterial multiplication was inhibited with tetracycline at various intervals after infection, and the subsequent clearance of pneumococci was determined. Viable pneumococci were rapidly killed by lung defenses if bacterial multiplication was inhibited within 12 h of the onset of infection. No change occurred in the bacterial populationif tetracycline was delayed until 24 h after infection, indicating that pneumococcal killing by lung defenses had ceased. This effect could be reproduced with the addition of pneumococcal capsular polysaccharide to the inoculum, which produced a dose-related inhibition of pneumococcal clearance. The clearance of S. epidermidis was not impaired in the presence of pneumococcal pneumonia or by administration of exogenous capsular polysaccharide. These data indicate that pneumococcal pneumonia causes a marked impairment in lung antipneumococcal defenses within 24 h of the onset of infection. This acquired defect in antibacterial defenses may be due to the accumulation of pneumococcal capsular material in the lungs of infected animals.

Animals

Persistence of Mycobacterium tuberculosis in sputum without chest roentgenographic evidence of active disease.

Mycobacterium tuberculosis has been isolated consistently from sputum over an 11-year period in an asymptomatic 64-year-old man whose chest radiographs show evidence of healed primary tuberculosis (Ranke complex) but no evidence of parenchymal disease. A lymph node-bronchial fistula associated with the Ranke complex is the likely site of active tuberculosis; however, repeated examinations of the upper and lower respiratory tract have been normal. We attribute the persistence of infection in our patient to erratic usage of antituberculous drugs.

Humans

Determinants of lung bacterial clearance in mice after acute hypoxia.

Net lung bacterial clearance in normal mice is determined by the balance of in vivo bacterial multiplication on the one hand, and the defense mechanisms of mucociliary clearance and phagocytosis and killing by the oxygen-dependent alveolar macrophage on the other. The bactericidal function of the macrophage is the major component of the defense mechanism. The effect of acute hypoxia on the defense mechanism was studied in mice exposed to aerosols of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae. Physical clearance was not impaired by acute hypoxia, and bacterial replication was not stimulated by the low oxygen atmosphere. Clearance of Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli was impaired during acute hypoxia due to decreased phagocytosis or killing by the alveolar macrophage. The important human pathogen Streptococcus pneumoniae was cleared normally in the presence of acute hypoxia. This observation suggests that an oxygen-independent clearance mechanism is important in lung defense against the pneumococcus. This may be a separate mechanism within the alveolar macrophage or a system as yet unidentified.

Aerosols

Determinants of lung bacterial clearance in normal mice.

The determinants of the lung clearance of Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus were studied in normal mice after exposure to an aerosol of viable bacteria and 99mTc-labeled dead bacteria. The fraction of bacteria in lungs that remained viable 4 h after exposure were: S. pneumoniae, 7.3%; K. pneumoniae, 121%; E. coli, 88.5%; S. aureus, 27.6%. The rate of physical removal of bacterial particles (Kmc) was determined from the change in lung 99mTc counts with time: Kmc ranged between 7 and 12%/h and and was similar in all species. The rate of mucociliary clearance and of intrapulmonary bacterial killing (Kk + Kmc) was calculated from the change in bacterial counts with time in animals that had received tetracycline to inhibit bacterial multiplication. Kk, the rate of intrapulmonary killing, was obtained by subtraction of Kmc from (Kk + Kmc). The calculated values for Kk were: S. pneumoniae, - 87%/h; K. pneumoniae, - 17%/h; E. coli, - 18%/h; S. aureus, - 22%/h. The rate of intrapulmonary bacterial multiplication (Kg) was estimated from the relationship of bacterial counts in tetracycline and nontetracycline-treated animals, assuming that tetracycline altered only Kg. Kg, expressed as the doubling time, was: S. pneumoniae, 310 min; K. pneumoniae, 217 min; E.coli, 212 min; S. aureus, infinity (no multiplication). The data indicate that the marked differences in the clearance of these species from the normal mouse lung result from the interaction of differing rates of in vivo bacterial multiplication and killing.

Aerosols

The radiographic resolution of Streptococcus pneumoniae pneumonia.

To determine the characteristics of the radiographic resolution of bacteremic Streptococcus pneumoniae pneumonia we examined serial chest roentgenograms in 72 patients. Consolidation disappeared in all patients by eight to 10 weeks; volume loss (9 per cent), plural disease (9 per cent), and stranding (19 per cent) often persisted beyond eight weeks. Resolution occurred earlier in patients less than 50 years old (P less than 0.05) and in the absence of alcoholism and underlying airways disease regardless of age (P less than 0.05). Delayed clearing occurred when these complicating factors were present in patients over 50. Lung cancer was not responsible for delayed resolution of pneumonia. We conclude that an appropriate interval for serial radiographic examinations after therapy for pneumococcal pneumonia is six weeks.

Aging

Pneumoconiosis among the activated-carbon workers.

The prevalence of respiratory symptoms and chest radiographic and spirometric abnormalities was assessed among 397 employees of an activated carbon plant. Definite radiographic findings of pneumoconiosis, consisting of p-type, rounded opacities in the lower lung fields without firbosis or coalescence, were present in 9.6% of men and were related to cumulative dust exposure. Lesser degrees of radiographic abnormality suggesting pneumoconiosis were present in 11% of men and 2% of women. Spirometric values were substantially lower in blacks than in whites. However, cumulative dust exposure was not an important determinant of pulmonary function in either race. Review of lung biopsy speciments that had been obtained previously in two employees revealed extensive carbon depositiion but minimal associated fibrosis. Prolonged inhalation of activated carbon dust leads to pulmonary deposition of carbon and raciographic signs of pneumoconiosis; such deposition has little, if any, effect on respiratory symptoms or pulmonary function.

Adult

The course of untreated Mycobacterium kansasii disease.

Four patients with Mycobacterium kansaii pulmonary infection were followed without treatment for 10 to 14 years after diagnosis. Although spontaneous resolution of active disease occurred 5 years after diagnosis in one patient, slowly progressive disease in the absence of significant symptoms was documented in 3 patients during a 12-to-14-year follow-up period. Administration of antituberculous drugs resulted in rapid resolution of signs of active disease in these patients. These observations added to our limited knowledge of the natural history of M. kansasii disease.

Adult