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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Discussion (3)

The question as to whether the PAM functional defect is a phenomenon reflecting the proximity of the immune effector cells to the tumor, or whether there is a generalized defect affecting PAMs in the opposite lung (and possibly also peripheral blood monocytes) was addressed in a group of five patients with cancer who underwent BAL of both cancer-bearing and noncancer-bearing lungs. Previously reported defects in lung natural killer cell activity have described this as a local tumor-related phenomenon not present in peripheral blood lymphocytes, and we suspected this might equally apply to the presently described macrophage-related defect, as it has been noted that macrophage chemotaxis decreases with increasing tumor proximity. Mean baseline cytostatic activity was not different between cancerous and noncancer-bearing lungs for the group and was again significantly lower than the baseline activity in our previously mentioned control group. This small pilot study suggests that the PAM abnormality is part of a generalized immune defect in patients with lung cancer and does not simply reflect a local response to the carcinoma. As the cytostatic defect can be overcome by administration of 7-interferon, we hypothesize that a defect of macrophage activation may underlie the macrophage dysfunction, thus implicating the T-cell, which is known to activate macrophages by its production of a variety of lympholdnes. Assays of blood and BAL 7-interferon may prove useful tools for testing this hypothesis in future studies, but have not been included in our work to date. buy antibiotics online
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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Discussion (2)

Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Discussion (2)We have shown that there is a defect of PAM activation for tumor cell cytostasis in patients with lung cancer and that this defect does not appear to be related to smoking, since when cytostatic activity was compared between current smokers, ex-smokers, and nonsmokers within each group, no significant differences were found. buy prednisone

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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Discussion (1)

The data presented herein suggest (a) that in vitro PAM baseline cytostatic activity is lower in patients with lung cancer than in control subjects; (b) that 7-interferon can significantly augment cytostatic function in patients with cancer, to levels comparable with those achievable in a nearly normal control group; and (c) that the PAM abnormality may be part of a generalized immune defect, rather than a specific response to local inhibitory substances produced by the tumor.
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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Results (3)

Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Results (3)Cytostatic Activity after y-Interferon Activation
In order to evaluate the reversibility of the defect in macrophage function, PAM cytostatic activity was compared within and between the groups after activation with 7-interferon. There was a significant increase in cytostatic function after stimulation with 7-interferon in the group with cancer (28 ± 5 percent increase from baseline) (Fig 2), while only a further small increase (5 ± 1 percent) was seen after stimulation in the control group, whose baseline activity was already well over 90 percent (p<0.0005 for comparisons of percentage changes between the groups). Thus, the cytostatic activity after 7-interferon was not significantly different between the groups; that is, 7-interferon activated PAMs from the group with cancer (data not shown). buy ampicillin

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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Results (2)

Baseline Cytostatic Activity
Baseline cytostatic activity was significantly lower (mean, 59 ±7 percent) in the group with cancer than in the control group (mean, 92 ± 2 percent) (p<0.0002) (Fig 1). This difference persisted when the patient with previously surgically treated cancer was excluded. The effect of smoking on cytostatic activity was analyzed using a Kruskall-Wallis one-way analysis of variance for nonparametric data. buy levaquin online
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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Results (1)

Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Results (1)Total cell counts were not different between the groups, and all patients had differential cell counts within the normal range. Mean differential (±SE) counts for the group with cancer (n = 14 out of 19) were as follows: macrophages, 95 ± 3 percent; lymphocytes, 5 ± 2 percent; neutrophils and eosinophils, each less than 1 percent. For the control group the counts were as follows: macrophages, 91 ± 2 percent; lymphocytes, 7 ± 1 percent; neurophils, 1 ± 0.4 percent; and eosinophils less than 1 percent.
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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Materials and Methods (4)

Cyto stasis Assay
This assay has been previously described using Teflon bag macrophages and monocytes.19 In brief, following incubation at 37°C for 24 hours, macrophage supematants were discarded, and tumor target cells (1 X lOVml) were added to the adherent macrophages. U937, a human histiocytic lymphoma cell line, was used as the target, as it has previously been shown to give reproducible results in this assay. Control wells of U937 alone were included, and the cells were incubated for 48 hours. U937 targets were then resuspended by vigorous pipetting, and 100|xl aliquots from each well were transferred to a new plate. The cells were pulsed for 6 h with 0.2fjiCi of tritiated thymidine (Amersham UK; 23 Ci/mmol), and the incorporated radioactivity was measured by liquid scintillation.
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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Materials and Methods (3)

Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Materials and Methods (3)Lavage fluid was aspirated, collected on ice, and transferred to polypropylene containers in order to minimize macrophage adherence. Straining through gauze was only rarely necessary to remove excess mucus. Recovered cells were counted, washed twice in PBS, and resuspended in RPM1-1640 medium containing 10 percent FCS and antibiotics. Total and differential cell counts were performed on cell spots stained using the Diff-Quick method.
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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Materials and Methods (2)

The group comprised 11 men and four women aged 34 to 82 years (mean, 64 years). Six patients underwent bronchoscopy for investigation of chronic cough. Two had suffered recent small hemopytses; five had chest radiographic opacities which were proven not be cancer (hamartoma; old granuloma); one patient underwent review bronchoscopy after previous removal of a foreign body; and one had unexplained dyspnea (with normal chest roentgenogram and pulmonary function tests). One patient was a current smoker, seven were ex-smokers, and seven had never smoked.
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Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Materials and Methods (1)

Defective Cytostatic Activity of Pulmonary Alveolar Macrophages in Primary Lung Cancer: Materials and Methods (1)Patients with Cancer
Nineteen patients with lung cancer were studied (18 men). Their mean age was 67 ±2 years (range, 44 to 75 years). In 18 patients the tumor was recently diagnosed and untreated; while in one subject, bronchoscopy was performed because of tumor recurrence after apparently complete resection one year previously. The tumor types were as follows: squamous cell carcinoma (ten); large-cell undifferentiated carcinoma (six); and adenocarcinoma (three). Six patients had stage 1 disease (potentially resectable tumor without nodal involvement), and 13 had stage 3 disease (including any T3,N2 or Ml tumor according to the TNM classification).1718 Seven patients were current smokers; ten were ex-smokers, and two were nonsmokers. Five of the patients underwent lavage of both lungs to assess whether any abnormality found reflected immune paresis related to tumor proximity or was part of a more generalized defect. buy diabetes drugs
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