Visible Lung Research Articles

Cadmium-induced lung injury: Cell kinetics and long-term effects

The effects of exposure to CdCl 2 aerosols followed by hyperoxia were studied in mouse lung. Special emphasis was placed on analysis of cell proliferation following injury. Male Balb c mice were exposed to aerosols of 4.9 μg Cd/liter for 1 hr while controls were exposed to water aerosols. Immediately after, half of each group was placed in 80% O 2 for 6 days, while the rest were left in room air. Three endpoints were used to assess lung injury; measurement of hydroxyproline, [ 14C]thymidine incorporation into DNA, and histopathology. Parenchymal and bronchiolar labeling indices were determined following autoradiography. A 1-hr exposure to CdCl 2 aerosols caused marked cell proliferation in the lung with the peak of cell labeling occurring at Day 5. In animals exposed to both CdCl 2 + 80% O 2, the cell labeling peak was delayed until Day 9. Cell differentiation studies showed a delay in the peak of type II epithelial cell and endothelial cell division when CdCl 2 exposure was followed by the 80% O 2 treatment. On Day 15 most of the labeled cells were identified as interstitial cells in both treated groups. Bronchiolar cell labeling was suppressed at the early time period in the Cd + O 2 group. With time, the histologically visible lung lesions tended to resolve in animals exposed to CdCl 2 or CdCl 2 and 80% O 2, whereas total pulmonary hydroxyproline remained at all times (3, 6, and 12 months) significantly higher in Cd-treated animals when compared to controls. It was concluded that acute lung injury by a toxic inhalant can be amplified if there is an initial delay in pulmonary cell proliferation following an acute insult.

A specific vaccine effective against stage I and stage II malignant disease in guinea pigs. Effect of variations in preparations and storage.

Guinea pigs, each with an established, syngeneic dermal line 10 tumor and lymph node metastases, were immunized by intradermal injection of a mixture of irradiated line 10 cells and an emulsion containing heat-killed BCG. Immunization eradicated 7- or 10-day-old dermal tumors (about 10 or 12 mm in diameter, respectively) and prevented growth of microscopic lymph node metastases. Fourteen-day-old dermal tumors (about 15 mm in diameter) were not rejected by immunization. Guinea pigs with stage II disease (21-day-old dermal tumors and palpable metastases in the first draining lymph node) were treated by excision of the dermal tumor and the first draining lymph node, and by specific immunization. This treatment eliminated tumor cells remaining in the second draining lymph nodes. The surgical treatment alone was not curative, palpable metastases in the second draining lymph nodes progressed and the animals died (some with visible lung metastases). Emulsions containing killed BCG were good adjuvants even after prolonged storage at 4 degrees C, but lost most of their adjuvant activity after autoclaving or freezing.

Treatment by limited surgery and specific immunization of guinea pigs with stage II experimental cancer.

The malignant disease produced in guinea pigs by intradermal inoculation of line-10 was allowed to progress to stage II, at which time the dermal tumor and the first draining lymph node were grossly evident. At that stage, the external appearance of the next draining lymph node was normal, but it contained tumor cells. Limited surgery consisting of excision of the dermal tumor and first draining lymph node was not curative; palpable metastases developed in the second and other draining lymph nodes, and at autopsy, some animals were found to have gross, visible lung metastases. Immunization of guinea pigs with a mixture of irradiated syngeneic tumor cells plus mycobacterial cell walls in an oil-in-water emulsion eradicated tumor cells remaining in lymph nodes after limited surgery for stage II experimental cancer and prevented progression of the disease to stage III. Tumor intravenously implanted in the lungs of animals after limited surgery for stage II disease was also eliminated by immunization.

Growth and Metastasis of Human Melanoma Xenografts in the Hamster Host<xref ref-type="fn" rid="FN2">2</xref>

Cells from three human melanoma cell culture lines (UCLASO-M-12, UCLASO-M-7, and WEG-1) were transplanted into the cheek pouches of immunosuppressed hamsters. Tumor nodules were found in the cheek pouches of hamsters receiving any one of these lines, and by 90--100 days after transplantation, nearly all hamsters had grossly visible lung metastases. Metastases were noted only in hamsters receiving continuous immunosuppression during the transplant period.

Correlation of Biochemical and Morphologic Manifestations of Acute Pulmonary Fibrosis in Rats Administered Paraquat

Rats were administered 24 mg/kg of paraquat intraperitoneally. One, two, three, six and seven days after this injection, the rats were evaluated by several toxicologic, biochemical, and morphologic criteria. These included determinations of weight loss, visible lung hemorrhage, pulmonary edema, <i>in vitro</i> protein and collagen biosynthesis rates of lung tissue, and staining properties of lung sections. Morphologic evidence of mild edema was seen at day 1, while more severe edema was observed at days 2 through 7. Weight loss was apparent from day 1 throughout the experiment. <i>In vitro</i> protein biosynthesis rates by tissue were elevated above control values from day 3 onwards, while collagen biosynthesis rates were elevated from day 2 onwards. Increased staining with the Gomori reagent was observed from day 1, while increased staining with van Gieson's or Masson's trichrome appeared by day 2 or 3.

Correlation of biochemical and morphologic manifestations of acute pulmonary fibrosis in rats administered paraquat.

Rats were administered 24 mg/kg of paraquat intraperitoneally. One, two, three, six and seven days after this injection, the rats were evaluated by several toxicologic, biochemical, and morphologic criteria. These included determinations of weight loss, visible lung hemorrhage, pulmonary edema, in vitro protein and collagen biosynthesis rates of lung tissue, and staining properties of lung sections. Morphologic evidence of mild edema was seen at day 1, while more severe edema was observed at days 2 through 7. Weight loss was apparent from day 1 throughout the experiment. In vitro protein biosynthesis rates by tissue were elevated above control values from day 3 onwards, while collagen biosynthesis rates were elevated from day 2 onwards. Increased staining with the Gomori reagent was observed from day 1, while increased staining with van Gieson's or Masson's trichrome appeared by day 2 or 3.

Serum factor levels during the growth of rat hepatoma nodules in the lungs

The levels of tumour-specific antigen, antibody and specific immune complexes in the sera of rats bearing lung nodules of a chemically induced rat hepatoma, produced by intravenous inoculation of viable tumour cells, have been examined and compared with the levels of serum factors in animals actively immunized by intravenous inoculation of mixed tumour cells and BCG. Animals inoculated with cells alone developed multiple lung nodules which slowly grew, until on day 24 the remaining animals had to be killed due to respiratory distress. In contrast, the animals receiving a mixed inoculum of BCG and tumour cells developed no visible lung nodules and were capable of rejecting a further challenge of tumour cells. Tumour-specific antigen could be detected in the sera of both groups of rats at different times. In actively immunized animals free antigen could be detected from day 3 to day 10 after inoculation of cells BCG whereas in animals receiving cells alone, free antigen could not be detected until day 14 and persisted until the termination of the experiment. Free tumour-specific antibody, however, was found in the sera of rats actively immunized with tumour cells and BCG from day 10 onwards, although in the other group of animals it could not be detected. Conversely, immune complexes of tumour-specific antigen and antibody could be detected from day 10 in rats receiving cells alone and only at day 10 in actively immunized rats. The relevance of these findings in relation to what is known about serum factor levels during tumour growth and regression is discussed.

Effect of lung irradiation on the incidence of pulmonary metastases and its mechanism.

LP-12 cells injected intravenously into ddY mice result in the formation of visible lung colonies which are introduced as a model for pulmonary metastases. Localized irradiation before tumour cell transplantation significantly increased the incidence of pulmonary metastases in the irradiated lung only. The changes of the vascular permeability of the lung indicate that dilatation of capillaries or increased permeability may be one of the main mechanisms of this phenomenon.

Radiation control of microscopic pulmonary metastases in C3H mice.

C3HBA adenocarcinoma cells injected intravenously into isogeneic C3H/HeJ mice result in the formation of visible lung colonies which are introduced as a model for pulmonary metastases. Visible lung colonies are both time dependent and injected cell number dependent. Control of the lung colonies at their microscopic (subclinical) stage is achieved by a single radiation dose of 2100 rads, which is far less than the dose necessary to control palpable primary tumors. An in vivo survival curve for the microscopic lung colonies irradiated with graded single doses is resented.

A correlated histological, cytological, and cytochemical study of the tracheobronchial tree and lungs of mice exposed to cigarette smoke. 3. Unaltered incidence of grossly visible adenomatous lung tumors in female CF mice after prolonged exposure to cigarette smoke.

A correlated histological, cytological, and cytochemical study of the tracheobronchial tree and lungs of mice exposed to cigarette smoke. 3. Unaltered incidence of grossly visible adenomatous lung tumors in female CF mice after prolonged exposure to cigarette smoke.

Development of Influenzal Complement-Fixing Antigen and Antibody in Mice.

The lungs of mice infected with the virus of epidemic influenza contain a soluble complement-fixing antigen which is separable from the virus., The purpose of the work here reported was to investigate the conditions under which this antigen and its corresponding antibody are formed. Mice were inoculated with the mouse passage strain PR8 of epidemic influenza virus in dilutions from 10-2 to 10-3 of lung. At different intervals of time from 1 to 10 days, 6 to 8 mice receiving each of the dilutions were killed by bleeding from the heart under chloroform anesthesia. The complement-fixing antigen was measured by titration of a saline suspension of the ground lung material against a constant dilution of 1:20 of a pool lof human convalescent serum according to the complement-fixation method previously described. The results are recorded in the accompanying table. One day after inoculation none of the mice showed macroscopically visible lung lesions, but the complement-fixing antigen was already present in relatively high titer except in the group receiving a dilution of 10-6. Between the second and fifth days the appearance of antigen at a maximum titer preceded by 2 to 3 days the maximum development of lung lesions. This suggests that the formation of the antigen is associated with a rapid multiplication of the virus before the appearance of the red pulmonary consolidation. With virus dilutions of 10-3 or above, the maximum titer of antigen seemed to be related to the amount of virus inoculated. In the lungs of mice inoculated with dilutions 10-5 and 10-8 and killed after 4 days, the antigen titered 1 :40 and 1 :20 respectively and no macroscopic lesions were found.