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Biomedical subjects

E C Lawrence

Publications and source records attributed to E C Lawrence.

At least 55 records · Page 3Linked to original sources
PubMed1986

In vitro cytotoxicity of chrysotile asbestos to human pulmonary alveolar macrophages is decreased by organosilane coating and surfactant.

Human pulmonary alveolar macrophages were used to quantitate the cytotoxic effect of surface-altered chrysotile asbestos. Little difference was observed in mortality between chrysotile asbestos that was surface-treated to a 42% extent by a hydrophobic organosilane or untreated chrysotile. Little or no effect on mortality was observed when human pulmonary alveolar macrophages were cultured with untreated chrysotile or acid-leached asbestos in the presence of 10 mM dipalmitoyl lecithin. However, when human pulmonary alveolar macrophages were cultured with a hydrophobically-treated (to a 42% or 95% extent) chrysotile asbestos in the presence of 10 mM dipalmitoyl lecithin, a statistically significant decrease in mortality was observed compared to untreated chrysotile. No mutagenic activity was observed when V79 cells were cultured with acid-leached, or 42% hydrophobically-treated chrysotile asbestos, even when human pulmonary alveolar macrophages were included as an activation source. The 95% hydrophobically-treated and acid-leached chrysotile also exhibited decreased binding of benzo[a]pyrene compared to untreated chrysotile asbestos.

Adult↗
PubMed1986

Permanent intrinsic B cell immunodeficiency caused by phenytoin hypersensitivity.

We report a patient who, 3 weeks after initiation of therapy, experienced a hypersensitivity reaction to phenytoin manifested as rash, lymphadenopathy, elevated serum transaminase levels, and subsequent panhypogammaglobulinemia with IgG, 180 mg/dl (control range 639 to 1349); IgA, 15 mg/dl (control range 70 to 312); and IgM, 0 mg/dl (control range 56 to 352). Repeated in vitro lymphocyte analysis documented normal T cell-mediated immunity including T cell surface markers (E rosettes), lymphocyte proliferation after mitogen stimulation, and T cell phenotypes (T4 or helper and T8 or suppressor cells). However, the patient had a paucity of circulating B-lymphocytes as assessed by the number of lymphocytes with surface membrane immunoglobulin (patient value of 0 compared to the control range 16 to 435 cells per microliter of blood) and by the number of lymphocytes bearing the B1 antigen (patient value of 13 compared to the control range 48 to 358 cells per microliter of blood). Hemolytic plaque assay revealed decreased immunoglobulin production (number of immunoglobulin-secreting cells per million circulating mononuclear cells) as compared to control subjects (patient unstimulated mean of 100 as compared to a control mean of 1753) and minimal enhancement on stimulation with pokeweed mitogen (patient stimulated mean of 250 as compared to control mean of 8946). Coculture experiments with the reverse hemolytic plaque assay revealed no evidence of suppression. No reversal of this patient's immunodeficiency has occurred 3 years after phenytoin withdrawal.

Adult↗
PubMed1986

Human alveolar lining material and antibacterial defenses.

To investigate the possible antibacterial properties of human alveolar lining material (ALM), we obtained ALM and pulmonary alveolar macrophages (PAM) by bronchoalveolar lavage of healthy nonsmokers. Alveolar lining material was isolated by centrifugation or micropore filtration; electron microscopy revealed lamellar bodies, and lipid analysis showed that 98% of the lipid fraction was phospholipid. No free fatty acids were detected. Streptococcus pneumoniae and non-typable Haemophilus influenzae (NTHI) died spontaneously in PBS at a mean rate of log10 0.75 and 0.95 in 90 min, respectively; the addition of ALM appeared to exert a slight protective effect, and at higher concentrations supported replication of NTHI. There was no difference in the uptake of the bacteria by PAM when ALM was present. Phagocytosed NTHI were killed rapidly and completely within 60 min by PAM with or without ALM. A greater proportion of S. aureus were killed by PAM alone than in the presence of ALM. Alveolar lining material from healthy humans thus appears to have no demonstrable effect on host defense against these bacteria. The differences between our results and those of earlier studies using ALM from rats may relate to interspecies differences in the composition of ALM.

Cholesterol↗
PubMed1986

Chemiluminescence of lung macrophages and blood leukocytes in sarcoidosis.

A luminol-enhanced chemiluminescence assay was used to measure light elaborated by peripheral blood polymorphonuclear leukocytes (PMNs) and by pulmonary alveolar macrophages (PAMs) from 14 healthy, normal subjects and 16 patients with sarcoidosis. Resting peripheral blood PMNs (incubated only in medium) from patients with sarcoidosis generated substantially more chemiluminescence than PMNs from normal control subjects (p = 0.002). With zymosan stimulation, greater chemiluminescence was produced by PMNs from untreated patients with sarcoidosis than from normal subjects (p less than 0.05), whereas no differences were noted with latex stimulation. Chemiluminescence for resting PAMs was not different between normal subjects and patients with sarcoidosis. However, PAMs from untreated patients with sarcoidosis had higher chemiluminescence with latex particle ingestion than PAMs from normal subjects (p less than 0.05), but no differences in PAM chemiluminescence were found when zymosan was the phagocytic particle. Increased chemiluminescence by PMNs and PAMs from patients with sarcoidosis may reflect phagocyte activation in the disease process.

Adult↗
PubMed1986

Palliation of bronchogenic carcinoma with 198Au implantation using the fiberoptic bronchoscope.

The majority of cases of bronchogenic carcinoma remain incurable, and many of these patients require palliation of the effects of the tumor on the airway. We have developed a technique for implanting radioactive (198Au) seeds via the fiberoptic bronchoscope. We now retrospectively review the results obtained in 111 procedures in 54 patients. Response was assessed by improvement in symptoms, chest roentgenogram, or bronchoscopic appearance. Nineteen of 29 (66 percent) patients with occluding endobronchial lesions benefitted. Twenty of 22 (91 percent) with hemoptysis improved. All six patients with tracheal lesions benefitted. Two of six (33 percent) patients with nonoccluding endobronchial lesions responded. Complications directly related to the procedure were rarely of major consequence, although a single patient had an exsanguinating hemoptysis four days following the last of multiple implantations. The simplicity, relative safety, and potential wide availability coupled with low equipment costs would suggest an increasing role for this technique in the palliation of endobronchial neoplasms.

Adult↗
PubMed1985

Phagocytosis and killing of common bacterial pathogens of the lung by human alveolar macrophages.

To investigate factors that determine susceptibility of the lungs to infection with common respiratory pathogens, we studied phagocytosis and killing of nontypable Haemophilus influenzae, H. influenzae type b, Streptococcus pneumoniae types III, VI, and XIV, an unencapsulated variant of S. pneumoniae type III, and Staphylococcus aureus Cowan I, by using human alveolar macrophages obtained by bronchoalveolar lavage of healthy nonsmokers. After opsonization with 10% pooled human serum, mean uptake (+/- standard deviation) of nontypable H. influenzae (67.5% +/- 15.0%), unencapsulated S. pneumoniae type III (71.2% +/- 4.8%) and S. aureus (79.1% +/- 10.2%) was significantly greater (P less than .01) than that of H. influenzae type b (40.1% +/- 15.0%), and S. pneumoniae types III (4.4% +/- 3.1%), VI (11.8% +/- 9.6%), or XIV (8.7% +/- 7.0%). Nontypable H. influenzae was ingested after opsonization with much less pooled human serum than was H. influenzae type b, and uptake of encapsulated S. pneumoniae was not enhanced by as much as 80% pooled human serum. Intracellular killing of unencapsulated S. pneumoniae type III and nontypable H. influenzae was rapid and complete and corresponded to the degree of phagocytosis, but despite a high uptake, S. aureus were killed slowly and incompletely. The virulence of S. pneumoniae and H. influenzae as lung pathogens is thus determined jointly by encapsulation and the inadequate opsonizing effect of normal human serum, whereas that of S. aureus may be related to the organism's relative resistance to intracellular killing by alveolar macrophages.

Antibodies, Bacterial↗
PubMed1984

Immunoregulation in an isolated 12-year-old boy with congenital severe combined immunodeficiency.

We report the evaluation of in vitro immunoregulation in a 12-year-old untreated boy with severe combined immunodeficiency (SCID). Severely hypogammaglobulinemic, the patient was incapable of a specific antibody response to either natural substances or administered antigens. Ficoll-Hypaque-isolated peripheral blood mononuclear cells (MNL) from the patient failed to respond to pokeweed mitogen (PWM) with the normal increment in immunoglobulin-secreting cells, as measured by a reverse hemolytic plaque assay. Since the patient was lymphopenic, his MNL were relatively enriched for monocytes (range = 51-81%). Removal of phagocytic cells or the addition of unrelated irradiated helper T lymphocytes resulted in enhanced, but still suboptimal response to PWM, suggesting some intrinsic defect in B lymphocyte function. Co-culture of patient MNL with normal MNL resulted in marked suppression (12% of predicted) of PWM-induced Ig-secreting cells. Suppressor activity was unaffected by prior irradiation of patient MNL, but was substantially reversed (99% of predicted) by removal of his phagocytic cells, whereas the combination of the two procedures further reversed suppression (184% of predicted). The patient's MNL consistently demonstrated subnormal percentages of T3+ and T4+ cells and subnormal to low normal percentages of T8+ cells. These data suggest both an intrinsic defect in B lymphocyte function, and a relative excess of monocytes which could further inhibit Ig secretion by B lymphocytes. Natural killer (NK) cell function was characterized by normal target cell binding by NK cells but severely depressed NK cell cytotoxicity.

B-Lymphocytes↗
PubMed1983

Serial changes in markers of disease activity with corticosteroid treatment in sarcoidosis.

Serial changes in various markers of disease activity with corticosteroid therapy were assessed in 12 patients with active sarcoidosis. After six weeks of treatment with 40 mg daily of prednisone, all but one patient demonstrated symptomatic and radiographic improvement. For the entire patient group, there were corresponding improvements in forced vital capacity, from 59.2 +/- 5.5 to 70.5 +/- 5.3 percent of the predicted value (p less than 0.001, Student paired t test), serum angiotensin-converting enzyme levels, from 66.0 +/- 12.1 to 28.2 +/- 4.0 U/ml (p = 0.003), 67gallium lung scanning scores, from 3.6 +/- 0.2 to 0.8 +/- 0.3 (p less than 0.001), serum gamma globulin levels, from 2.40 +/- 0.2 to 1.5 +/- 0.1 g/dl (p less than 0.001), and erythrocyte sedimentation rate, from 26.8 +/- 2.7 to 14.8 +/- 3.0 mm per hour (p less than 0.001). Changes in percent of bronchoalveolar lavage fluid lymphocytes were less impressive (from 28.7 +/- 4.9 to 21.2 +/- 5.1, p = 0.034), but the geometric mean number of bronchoalveolar lavage fluid-IgG-secreting cells decreased from 23,861 to 3,830 (p = 0.013). Serial evaluations in five patients treated with decreasing doses of alternate-day prednisone for an additional 10 1/2 months indicated that changes in 67gallium lung scanning scores corresponded most closely to the clinical course in five of five patients. Determination of serum angiotensin-converting enzyme levels also closely paralleled the clinical course in four of five patients, whereas the other parameters measured were more variable markers of clinical response. However, abnormalities of bronchoalveolar lavage fluid-IgG-secreting cells often persisted in the absence of clinically evident disease, and the percentages of bronchoalveolar lavage fluid lymphocytes were frequently normal in patients who responded subsequently to corticosteroids. Larger prospective studies are warranted to more extensively evaluate various measurements of disease activity, especially bronchoalveolar lavage fluid analysis, in sarcoidosis.

Adult↗
PubMed1982

Modulation of pokeweed-mitogen-induced immunoglobulin secretion by human bronchoalveolar cells.

The effects of human bronchoalveolar cells on pokeweed-mitogen-induced immunoglobulin(Ig) secretion in vitro were investigated, using a reverse hemolytic plaque assay. Unfractionated peripheral blood mononuclear cells from 7 nonsmoking normal subjects responded to pokeweed mitogen with a geometric mean of 6,550 Ig-secreting cells per million cultured mononuclear cells, whereas monocyte-depleted mononuclear cells responded with only 148 (p = 0.015, paired 2-tailed t test). The addition of 1 to 20% autologous bronchoalveolar cells to unfractionated mononuclear cells progressively suppressed the Ig-secretory response (p less than 0.01, paired t test comparing 0 to greater than or equal to 10% added bronchoalveolar cells). However, the addition of low concentrations of bronchoalveolar cells to monocyte-depleted mononuclear cells partially reconstituted the response to pokeweed mitogen, whereas the response with higher concentrations of bronchoalveolar cells was similar to background responses. Thus bronchoalveolar cells could modulate pokeweed-nitrogen-induced Ig secretion in different ways, depending on the pressure or absence of monocytes in the mononuclear cell population. The suppressor activities of bronchoalveolar cells were not abrogated by prior irradiation and were only partially reversed by the addition of indomethacin to the cultures. However, prior disruption of bronchoalveolar cells completely abolished their suppressive functions. Suppression of pokeweed-mitogen-induced Ig secretion is probably mediated by intact, radioresistant pulmonary alveolar macrophages.

Adult↗
PubMed1982

Defective immunoglobulin secretion in response to pokeweed mitogen in sarcoidosis.

We studied in vitro immunoregulation of immunoglobulin (Ig) secretion in 21 patients with sarcoidosis. While peripheral blood mononuclear cells from normal individuals responded to pokeweed mitogen with a 10-fold or greater increment in Ig-secreting cells, cells from sarcoid patients failed to respond to pokeweed mitogen at any concentration employed (P less than 0.001, Student's t-test, two-tailed). More monocytes were found in sarcoid mononuclear cell preparations (44.8 +/- 2.0% vs 30.4 +/- 1.4% in normal donors, P less than 0.001), but removal of monocytes improved the response to pokeweed mitogen in only four patients. Mononuclear cells from seven of 19 patients suppressed Ig secretion in co-cultures with normal donor cells. Patients exhibiting excessive suppressor cell function were older, with longer standing and less clinically active disease than non-suppressing patients. Monocyte removal reversed the suppression in only four of the suppressor patients, but excessive suppressor monocyte function was later demonstrated in two sarcoid patients whose cells initially did not suppress Ig secretion when cultured with normal cells. While the immunological defects in sarcoidosis may be complex, heterogenous, and dynamic, these data suggest that suppressor monocytes, when present in sarcoidosis, may have developed secondarily.

Adult↗
PubMed1982

Alteration of in vitro immunoglobulin secretion by amosite asbestos.

We investigated the in vitro effects of amosite asbestos on immunoglobulin (Ig) secretion by human peripheral blood mononuclear leukocytes (MNL). Concentrations of 100 to 300 micrograms/ml of amosite asbestos reduced the number of Ig-secreting cells recovered from 6-day cultures of unstimulated MNL or MNL stimulated with Epstein Barr virus. By contrast, the Ig secretory response to pokeweed mitogen was enhanced by 10 to 100 micrograms/ml concentrations of amosite asbestos; however, amosite asbestos no longer enhanced the response to pokeweed mitogen when MNL were first partially depleted of monocytes (to less than 2%) esterase-positive cells remaining). These results indicate that amosite asbestos has multiple effects on the cells involved in Ig secretion: 1) amosite asbestos inhibits unstimulated B cell function; 2) amosite asbestos inhibits the function of B cells stimulated with the direct B cell activator Epstein Barr virus; and 3) amosite asbestos may alter regulator monocyte function allowing enhanced Ig secretion in the presence of monocyte-dependent B cell triggers such as pokeweed mitogen.

Antibody Formation↗
PubMed1981

Ontogeny of humoral immune function in normal chickens: a comparison of immunoglobulin-secreting cells in bone marrow, spleen, lungs and intestine.

A reverse haemolytic plaque was employed to study the ontogeny of immunoglobulin (Ig) secreting cells of either IgG, IgA, or IgM class in normal chickens. After hatching, IgM-secreting cells were detectable in the spleen by 3 days of age whereas IgG- and IgA-secreting cells were first noted at 6 days. Adult levels of Ig-secreting cells of all three classes were attained by 31 days of age in bone marrow and two separate lymphoid populations (lamina propria and intraepithelial lymphocytes). By contrast, adult levels of Ig-secreting cells were not obtained in either the spleen or the lungs until after 50 days of age. In the case of the spleen, the delay in attainment of adult levels of total Ig-secreting cells reflected the smaller spleen size in immature birds, whereas the percentages of cells secreting Ig of each class were in the adult range by 31 days. By contrast, the numbers of cells recovered from the lungs of 50-day-old chickens were near the adult range, while the percentages of cells secreting either IgG, IgA, or IgM were much fewer than those seen in the lungs of adult chickens. These data indicate that the lungs of normal chickens are populated more slowly with Ig-secreting cells than either the bone marrow, spleen, or intestine. At all ages studied, greater numbers of Ig-secreting cells, particularly of the IgG and IgM classes, were recovered from the bone marrow and spleen as compared to the lungs and intestine. Since only a portion of the total bone marrow population was studied, these data include that the bone marrow may be a major site of Ig-secreting cells in chickens beginning shortly after hatching.

Aging↗