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Biomedical subjects

L C Ginns

Publications and source records attributed to L C Ginns.

At least 37 records · Page 2Linked to original sources
PubMed1994

Expiratory flow pattern following single-lung transplantation in emphysema.

In single lung transplantation (SLT) recipients, a "plateau" of the maximal expiratory flow volume curve (MEFV) and a "biphasic" MEFV have been reported to reflect anastomosis pathology. A plateau is defined as constant airflow over a large expired volume early in the MEFV. A biphasic MEFV has an initial period of high flow followed by a terminal low flow phase. Models of expiratory flow limitation by wave speed, however, predict that the MEFV of SLT recipients with emphysema should both be biphasic and demonstrate a plateau even without anastomosis pathology. Review of the spirometries and clinical courses of our first ten patients receiving SLT for emphysema demonstrated a biphasic MEFV, and a plateau of the MEFV in all patients. No patient showed evidence of anastomosis pathology. Independent lung spirometries, generated by a novel technique, revealed that the initial high flow phase of the MEFV came from the transplanted lung and the terminal low flow from the native emphysematous lung. The location of the flow limitation was demonstrated to be immediately downstream from the anastomosis. Therefore, the MEFV of SLT recipients with emphysema routinely demonstrates both a biphasic pattern and a plateau, neither of which necessarily reflect anastomosis pathology.

Bronchoscopy↗
PubMed1992

T-cell alveolitis in lung lavage of asbestos-exposed subjects.

In sarcoidosis and idiopathic pulmonary fibrosis, it has been reported that lymphocyte proportions in lung lavage predict the subsequent clinical course. Recent evidence has suggested that lymphocytes are important in the alveolitis of asbestosis. We hypothesized that a greater relative proportion of T-lymphocytes in lung lavage of asbestos-exposed subjects is associated with immune activation and may predict the subsequent clinical course. We assessed lymphocyte subsets in lung lavage and peripheral blood (PB) of 97 asbestos-exposed subjects and 10 unexposed normal, using flow cytometry analysis of monoclonal antibody-treated cells. T-cell alveolitis was defined as follows: [%lymphocytes in lavage x %CD3 in lavage] greater than 2 SD above that product in normals. Eighteen subjects had T-cell alveolitis (group 1) and 79 did not (group 2). There were no significant differences between the groups in age, smoking status, duration of exposure, lung function results, or frequency of plaques or profusion greater than or equal to 1/0. Percent CD2 was higher in lavage of group 1 compared with group 2. There was a trend for higher %Ia in lavage of group 1 compared with group 2. These results identify a subgroup of asbestos-exposed subjects with T-cell alveolitis but no present excess of asbestos-related disease who may be at risk for future asbestos-related disease.

Adult↗
PubMed1991

Asbestos exposure and asbestos-related pleural and parenchymal disease. Associations with immune imbalance.

The study hypothesis was that asbestos exposure and asbestos-related pleural plaques and interstitial disease are associated with (1) immune imbalances favoring helper-inducer T-cell subsets in blood and bronchoalveolar lavage (BAL) and (2) T-lymphocyte accumulation in BAL. One hundred twenty-two asbestos-exposed subsets (AES), including 27 nonsmokers (NS), were evaluated and compared with 10 unexposed normal subjects. Data were collected on medical, smoking, and occupational histories, physical examination, spirometry, lung volumes, single-breath DLCO, chest films read by a "B" reader, and T-lymphocyte characterization in blood and BAL using flow cytometry analysis of monoclonal-antibody-treated cells. On average, AES were 47 yr of age and had 23 yr of asbestos exposure. Fifty-eight (48%) had pleural thickening, and seven (6%) had profusion greater than or equal to 1/0. In blood, asbestos-exposed NS had lower total and percent CD8 and lower total CD3 than did normal subjects. In BAL, asbestos-exposed NS had higher total CD3 than did normal subjects. Among AES, increased asbestos exposure was associated with increased percent CD8 in BAL and decreases in both percent lymphocytes and total CD8 in blood. Increase in CD4/CD8 ratio in BAL were associated with pleural thickening. In those seven with profusion greater than or equal to 1/0, there was increased percent CD4 in blood and decreased percent CD8 in BAL. These results suggest immune imbalance favoring helper-inducer T-cell subsets in association with asbestos exposure systemically and with pleural plaques in BAL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Practice patterns in the treatment of acutely ill hospitalized asthmatic patients at three teaching hospitals. Variability in resource utilization.

STUDY OBJECTIVE: Our objective was to determine the extent to which patterns of diagnostic and therapeutic practice differ among hospitals caring for acutely ill hospitalized asthmatic patients in a single city. DESIGN: Our study comprised a retrospective review of the records of patients admitted to the hospital for the treatment of acute asthma. SETTING: Three large teaching hospitals in Boston were the setting. PATIENTS: One hundred twenty-seven patients between 18 and 50 years of age who were admitted to the medical services specifically for the treatment of asthma were studied. INTERVENTIONS: There were no interventions. MEASUREMENTS AND MAIN RESULTS: For this group of patients with similar histories of asthma, clinical presentation, and severity of asthma, the diagnostic tests used within 12 hours of admission and the frequency and volume of diagnostic laboratory testing throughout the admission differed significantly among the three hospitals. Spirometry, the test bearing most directly on the severity of the asthmatic attack, was not used routinely as a criterion for admission or discharge at any of the hospitals. Other tests of uncertain efficacy, such as chest x-ray films, were used frequently at some of the hospitals. Patients at all three hospitals were treated similarly with intensive combined regimens of methylxanthines, sympathomimetics, and corticosteroids and had similar mean lengths of stay. The use of chest physical therapy, which has not yet been demonstrated to be effective in acute asthma, differed significantly among the three hospitals. CONCLUSIONS: We conclude that considerable variability exists in the diagnostic evaluation of acutely ill hospitalized asthmatic patients in the three hospitals; little variability exists in the pharmacologic treatment of these patients. In the absence of data on outcome regarding functional improvement and reductions in morbidity, we are unable to recommend a preferred pattern of practice from this study.

Acute Disease↗
PubMed1990

Elevated concentration of soluble interleukin-2 receptors in serum of smokers and patients with lung cancer. Correlation with clinical activity.

Soluble interleukin-2 receptor (sIL-2R) levels in cigarette smokers and in patients with lung cancer were measured using an enzyme immunoassay. The rationale for our study was based on the fact that activation of T-cells is dependent upon the T-cell growth factor, interleukin-2, which may be regulated by its receptor, IL-2R. Measurements of circulating sIL-2R might be useful in the immune assessment of certain conditions. This study assessed elevated concentrations of circulating sIL-2R in smokers and in patients with lung cancer. The data show that healthy smokers, as a group, have an elevated level of sIL-2R compared with that in nonsmokers. Significantly higher than normal levels were found among light, moderate, and heavy smokers. Patients with lung cancer (squamous cell carcinoma [SSC] or adenocarcinoma [AC]) also have abnormally high sIL-2R levels. In the SCC group, the highest level of sIL-2R was among asymptomatic patients with well-differentiated tumors. Similarly, patients with SCC whose tumors were less than 3 cm in diameter had a significantly higher mean level of sIL-2R than did patients whose tumors exceeded 3 cm. The sIL-2R level in the SCC group also correlated with the tumor stage, with the highest level found among Stage I patients. In patients with SCC, but not in those with AC, the sIL-2R level was indicative of the extent of malignancy. These data support the concept that sIL-2R may be important in the pathogenesis of immune alterations associated with smoking and lung cancer.

Adenocarcinoma↗
PubMed1990

Natural killer activity is present in rat lung lavage and inhibited by lidocaine.

Natural killer (NK) cells play an important role in defense against tumors and certain infected cells. Although NK activity is present in cells recovered from lung parenchyma, its demonstration in cells retrieved from normal bronchoalveolar lavage (lung lavage) has been difficult. In this study, we report that NK cells are present and active in normal rat lung lavage. Purified effector cells retrieved from lung lavage and peripheral blood mononuclear cells were compared for NK activity. NK activity was tested in a four hour 51-chromium release assay against radiolabeled Yac-1 target cells and expressed as lytic units (LU). There was no difference in NK activity between the blood and lung (80 +/- 10 LU vs. 62 +/- 15 LU). Since lidocaine is used in lung lavage for topical anaesthesia in humans and to increase the cell yield in animals, we also sought to determine if it could affect NK activity. We found that lidocaine inhibited NK activity in a dose dependent manner when it was instilled into the airways prior to performance of lavage. Lidocaine did not affect the yield of cells recovered from lavage, their relative proportions, nor their viability. Lung macrophages (93 +/- 1% nonspecific esterase positive) inhibited blood NK activity, an effect significantly augmented by lidocaine. In sum, we report that NK activity in lung lavage is similar to that found in blood and may be regulated by alveolar macrophages and that topical lidocaine inhibits NK activity, an effect which needs to be considered in studies of these cells from lung lavage.

Animals↗
PubMed1990

Effect of lidocaine on natural killer activity: rapid inhibition of lysis.

We have previously found that NK cell activity is present in rat lung lavage and inhibited by lidocaine. The purpose of this report is to characterize further the inhibition by lidocaine on NK activity. Peripheral blood lymphocytes from normal human volunteers were assayed in a four-hour 51chromium release assay in the presence of varying concentrations of lidocaine during or prior to the lytic assay. During the assay, increasing concentrations of lidocaine inhibited NK activity. This effect was not related to pH and at high concentrations was unrelated to methylparaben found in topical lidocaine. Preincubation of effector cells for one hour with different concentrations of lidocaine produced similar results which were temperature dependent and related to incubation time. Preincubation of effector cells in lidocaine (0.5g%) for one to ten minute intervals at 37 degrees C resulted in 60 to 92% inhibition, respectively. The lidocaine did not alter effector cell viability nor did it affect the phenotypes of the effector cells as determined by flow cytometry. Lidocaine's inhibition of NK activity remained the same for cells which were further purified by plastic adherence, nylon wool filtration and percoll density centrifugation. The effect was not reversed by a 16 hour incubation in tissue culture medium. In a single cell assay, we determined that the inhibition was at the level of cell lysis.

Adult↗
PubMed1987

Analysis of T cell subsets in normal adults. Comparison of whole blood lysis technique to Ficoll-Hypaque separation by flow cytometry.

Analysis of peripheral blood T cells and T cell subsets by immunofluorescence and flow cytometry is employed commonly in studies of normal individuals and in certain disease states. Methods for separating T cells from granulocytes and erythrocytes vary. We have sought to determine whether or not such procedures alter the composition of cells being analyzed. In this communication, we report that, in normal individuals, Ficoll-Hypaque separation of lymphocytes selectively decreases the OKT8+ subset compared to the whole blood lysis technique (P less than 0.01). The decrease in the OKT8+ subset results in a significant increase (P less than 0.01) in the OKT4/OKT8 ratio. This disparity appears to be due to a selective loss of OKT8+ cells during centrifugation over Ficoll-Hypaque. With the Ficoll-Hypaque method, we have also found that the fixation of lymphocytes reacted with monoclonal antibodies is less stable than cells prepared by the whole blood lysis method. The interpretation of measurements of T cell subsets is influenced by the method by which these cells are isolated.

Adult↗
PubMed1986

Pulmonary function in normal subjects and patients with sarcoidosis after bronchoalveolar lavage.

To determine if fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage impairs pulmonary function in normal subjects or those with sarcoidosis, we measured flow-volume loops, thoracic gas volume, and single breath carbon monoxide diffusing capacity before, one half hour and 24 hours after lavage. We studied 12 normal subjects; six underwent a large volume lavage (approximately 500 ml saline instilled), and six underwent a small volume lavage (approximately 175 ml). Five subjects with sarcoidosis also had a small volume lavage. Six control subjects underwent FOB without lavage. The FOB alone produced no significant changes in pulmonary function one half hour after the procedure. Small volume lavage in normal subjects produced no change except for a 16.3 +/- 5.1 percent (mean- +/- SEM) decline in peak expiratory flow rate (p less than .05) one half hour postlavage which returned to normal by 24 hours. This contrasts with sarcoidosis subjects in whom forced expiratory volume in one second, peak expiratory flow rate, and vital capacity declined by 20 +/- 4.8 percent, 26.7 +/- 7.3 percent, and 15.2 +/- 4.1 percent, respectively, (all p less than 0.05) one half hour postlavage. No change occurred in total lung capacity or diffusing capacity. Only with large volume lavage did decrements in lung function occur in normal patients that were comparable to those seen in the sarcoidosis subjects. Our findings suggest that bronchoalveolar lavage in normal patients can be associated with a significant and volume-related decline in pulmonary function and that in subjects with sarcoidosis, the deterioration is more pronounced.

Adult↗
PubMed1985

Natural killer cell activity in cigarette smokers and asbestos workers.

In order to evaluate the effects of cigarette smoking and asbestos exposure on cellular immunity, we tested a group of cigarette smokers and asbestos workers for natural killer (NK) activity in the peripheral blood. The mean NK activity in cigarette smokers was lower than in normal subjects (13.7 +/- 1.6 versus 29.0 +/- 3%; p less than 0.05). As a group, the mean NK activity for the asbestos-exposed group was also reduced compared with that of the nonsmoking control group (22.6 +/- 3.2%; p less than 0.05). When divided according to the smoking status, the asbestos workers who were nonsmokers or ex-smokers showed similar decreases in NK activity compared with normal subjects (19.5 +/- 6.2 and 21.2 +/- 4.5%, respectively; p less than 0.05). A subgroup of asbestos-exposed subjects who currently smoked showed no decrease in NK activity. The data show that NK activity is reduced in the peripheral blood of cigarette smokers and asbestos workers. The relatively normal NK activity found in asbestos workers who also smoked is unexplained. Impairment of NK activity is a potential mechanism for the increased incidence of infection and cancer in smokers and neoplasia in asbestos workers.

Adult↗
PubMed1983

Extent of squamous cancer of the lung correlates with alterations in circulating T cells.

In the present study we have assessed the effect of tumor size, node involvement, and overall extent of disease on the circulating T-cell profile. The effect of cigarette smoking was taken into account by covariate analysis. Compared to normal controls, the T-cell profile for a group of patients with limited disease is only different when evaluated on the basis of lymph node involvement. If lymph nodes were clinically uninvolved by tumor, there was an increase in total lymphocytes with an increase in total OKT3+ and OKT8+ lymphocytes. There was a decrease in percentage, but in total number of OKT4+ cells. The OKT4+/OKT8+ ratio was reduced. The T-cell profile for patients with extensive disease demonstrated a rise in WBC and an increased total lymphocyte count secondary to an increase in OKT3+ and OKT8+ cells. These findings were primarily owing to the T3 tumor classification, which indicates gross extension. The major difference between the limited disease and extensive disease groups appeared to depend upon whether or not the lymph nodes were involved by tumor. In the patients with positive lymph nodes there was a decreased percentage as well as absolute number of OKT8+ cells. As a group, therefore, these patients appeared different from those with limited disease on the basis of a high OKT4+/OKT8+ ratio. Therefore, monitoring of the T-cell profile in these patients may be useful in assessing disease activity.

Antibodies, Monoclonal↗
PubMed1983

Asbestos exposure correlates with alterations in circulating T cell subsets.

Peripheral blood lymphocytes were analysed from 40 subjects with occupational asbestos exposure and 40 controls matched for age and smoking habits. Patients were classified by duration of exposure as short or long, and by chest radiograph as normal, pleural plaques or interstitial changes. As a group, subjects with asbestos exposure had decreased percentages of OKT3+ and OKT8+ cells and increased OKT4+/OKT8+ ratio compared to controls. Correcting for age and smoking, those with short exposure were similar to controls, while those with long exposure had decreased percentages OKT3+ and OKT8+ cells and an increased OKT4+/OKT8+ ratio. Among radiographic subgroups, those with normal radiographs were similar to controls, but those with plaques had increased circulating OKT4+ cells, and those with interstitial changes had decreased percentages OKT3+ and OKT8+ cells and OKT8+ cells/mm3, with an increased OKT4+/OKT8+ ratio. There were no differences between subjects and controls in OKT10+ cells and OKIa+ cells. There appears to be a progressive decrease in percentage OKT8+ cells and increase in OKT4+/OKT8+ ratio with increasing exposure to asbestos, as determined by length of exposure and by radiographic abnormalities.

Antibodies, Monoclonal↗
PubMed1982

T-lymphocyte subsets in smoking and lung cancer: Analysis of monoclonal antibodies and flow cytometry.

In order to determine whether abnormalities of immunoregulatory T-cells occur in patients with lung cancer, we characterized peripheral T-lymphocytes in 26 patients with untreated lung cancer. The results in patients with primary squamous cancer (SC) (n = 10), primary adenocarcinoma (AC) (n = 7), and secondary lung metastases (M) (n = 9) were compared with each other and to subjects without cancer (n = 48), including nonsmokers (n = 29) and smokers (n = 19). We found that OKT3+ (mature, peripheral (T-lymphocytes, including both OkT4+ (inducer/helper) and OKT8+ (cytotoxic/suppressor) lymphocytes, were increased in light-to-moderate smokers, but that OKT4+ cells were decreased n heavy smokers (p less than 0.05). The ratio of OKT4+ to OKT8+ (4/8) lymphocytes, reflecting the balance of immunoregulatory cells, was normal in light-to-moderate smokers, but was decreased in heavy smokers (p less than 0.05). The profile of circulating T-cells in patients with SC was similar to the smokers. In contrast, in patients with AC, we found a decreased percentage of OKT8+ cells (p less than 0.05). The 4/8 ratio was elevated in patients with AC (p less than 0.05). In patients with M, there was a decreased percentage of OKT3+ cells reflected in both OKT4+ and OKT8+ subsets. The 4/8 ratio in patients with M was low. Thus, a number of abnormalities in circulating T-cells was found both in smokers and in patients with lung cancer. These results suggest that immunoregulatory abnormalities contribute to the pathogenesis of lung cancer.

Adenocarcinoma↗
PubMed1982

Reversible alterations in immunoregulatory T cells in smoking. Analysis by monoclonal antibodies and flow cytometry.

We characterized T-lymphocyte subsets in peripheral blood of smokers (N = 60) and nonsmokers (N = 35). Total T-lymphocytes and T cell subsets were similar to nonsmokers in light and moderate smokers. In heavy smokers, total OKT3+ cells were increased, the percentage of OKT4+ cells was decreased, and percentage and total number of OKT8+ cells were increased. The ratio of OKT4+ to OKT8+ lymphocytes was decreased in heavy smokers. The percentage of OKT8+ cells and the OKT4+/OKT8+ ratio returned to normal in heavy smokers six weeks after they stopped smoking. These findings suggest that cigarette smoking causes reversible alterations in immunoregulatory T cells.

Adult↗
PubMed1978

Periodic loss of reactivity of a myeloma tumor with cytotoxic thymus-derived lymphocytes.

During each transplantation passage of a line of mouse myeloma tumor MOPC-315 through syngeneic (BALB/c) hosts, the tumor cells lose reactivity with cytotoxic thymus-derived lymphocytes directed against products of the BALB/c major histocompatibility complex (H-2d) and regain reactivity on transfer to fresh hosts. In contrast to this cyclical change, the tumor cells remain uniformly reactive with anti-H-2d alloantisera throughout the transplantation cycle.

Animals↗