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J H Butterfield

Publications and source records attributed to J H Butterfield.

69 records · Page 4Linked to original sources
PubMed1990

Sequestration of eosinophil major basic protein in human mast cells.

Previous studies showed that lung and skin mast cells do not contain eosinophil granule major basic protein (MBP). However, MBP has been localized by immunofluorescence to mast cells from a recently established human mast cell line. Analysis of MBP in human mast cell-1 cell lysates by radioimmunoassay showed immunochemical similarity to eosinophil MBP as judged by comparison of dose-response regression lines. Based on these findings and other new information about mast cell heterogeneity, we tested whether mast cells contain MBP. Mast cells were preserved in Carnoy's fixative and were identified by staining with rhodamine-conjugated avidin or for chloroacetate esterase or aminocaproate esterase activity. MBP was localized by immunofluorescence to mast cells in 6 of 7 nasal polyps, 4 of 4 ileal tissue specimens, and 12 of 14 cutaneous mastocytosis specimens. Furthermore, by immunoelectron microscopy MBP was localized to mast cell granules in cutaneous mastocytosis lesions. In contrast, normal skin mast cells preserved in Carnoy's fixative did not contain MBP. After injection of MBP into normal skin and fixation in Carnoy's fluid, mast cells became MBP-positive within 3 minutes, suggesting that endocytosis of MBP by mast cells had occurred. These results suggest that human mast cells in several tissues may sequester toxic eosinophil proteins by endocytosis.

Blood Proteins↗
PubMed1989

In vitro sensitivity of immature human mast cells to chemotherapeutic agents.

Cells from the human immature mast cell line, HMC-1, were tested for their sensitivity to 11 chemotherapeutic agents by changes in viability and incorporation of tritiated thymidine ([3H]-thymidine) after 72 h of in vitro drug exposure. Doxorubicin hydrochloride and cytosine arabinoside were the most active agents against HMC-1 cells at the concentrations tested. Doxorubicin hydrochloride inhibited the incorporation of [3H]-thymidine and decreased the viability of HMC-1 cells by greater than 90% at a concentration of 0.06 microgram/ml. Cytosine arabinoside inhibited the incorporation of [3H]-thymidine and decreased the viability by greater than 95% at a concentration of 0.1 microgram/ml. A clone of HMC-1 cells, A4, with an enhanced percentage (70-80%) of metachromatically staining cells was equally sensitive to these two agents; however, A4 cells were more sensitive to vinblastine sulfate and less sensitive to methylprednisolone than was the parent cell line. Both HMC-1 cells and A4 cells showed approximately equal sensitivity to etoposide and to mitomycin. These results show that human mast cells are susceptible in vitro to a number of commonly used chemotherapeutic drugs.

Antineoplastic Agents↗
PubMed1988

Mast cell pharyngitis as a cause of supraglottic edema.

A 30-year-old nonatopic woman had experienced a 9-year history of persistent symptoms of supraglottic edema. She had previously undergone epiglottectomy and excision of redundant left arytenoid tissue to improve her breathing and dysphagia. Uvular tissue was removed surgically at our clinic for histopathological examination of the excised tissues. This revealed diffuse infiltration by mast cells, many of which appeared degranulated. Uvular tissue from control patients undergoing uvulopalatopharyngoplasty for obstructive sleep apnea contained significantly fewer mast cells per high power field. To our knowledge such a degree of mast cell infiltration into supraglottic tissues has not been reported previously or associated with clinical symptoms.

Adult↗
PubMed1988

Establishment of an immature mast cell line from a patient with mast cell leukemia.

A cell line showing many characteristics of immature mast cells has been established from the peripheral blood of a patient with mast cell leukemia. Cultured cells contain low levels of histamine, are stained metachromatically by toluidine blue, and contain chloroacetate esterase, aminocaproate esterase and tryptase activities. The cells lack T and B lymphocyte, as well as myeloid cell markers, and do not possess IgE receptors. Solid tumors of metachromatically positive cells have been successfully induced and serially passed in nude mice using 5-azacytidine transformed cells. This cell line may be useful for future studies of mast cells and their constituents.

Animals↗
PubMed1986

Giant eosinophil colonies from cultures of bone marrow cells.

To date, the small size and slow growth of eosinophil colonies in vitro has hampered study of cloned eosinophils. We found enhanced eosinophil colony size and numbers in methylcellulose cultures of bone marrow cells utilizing defined supplemented bovine calf serum (DSBCS) in combination with EL4 conditioned medium (EL4-CM). At days 9, 16 and 23 significantly more eosinophil colonies and more cells/colony were present in cultures incubated with DSBCS/EL4-CM than in cultures incubated with fetal calf serum/EL4-CM. The ability to generate large numbers of eosinophils in vitro should facilitate study of cloned eosinophils.

Bone Marrow Cells↗
PubMed1986

Effects of glucocorticoids on eosinophil colony growth.

The in vivo and in vitro effects of glucocorticoids on eosinophilopoiesis were examined with soft agar cultures of bone marrow and peripheral blood cells. Prednisone, 10 mg four times daily for three days, administered to normal volunteers, caused a significant drop in circulating eosinophil numbers (p less than 0.005) but did not decrease eosinophil colony numbers in cultures of bone marrow or peripheral blood. A patient with peripheral blood eosinophilia demonstrated a larger percentage decrease in mean eosinophil colony numbers (50%) after prednisone than did any normal volunteer. Incubation of bone marrow cells for 1 hour with either high concentrations of hydrocortisone, up to 3.3 X 10(-4) mol/L, or with postinfusion plasma from volunteers administered intravenous hydrocortisone, plasma levels to 1.6 X 10(-5) mol/L, did not decrease the numbers of eosinophil colonies. At a concentration of 3.3 X 10(-6) mol/L of hydrocortisone, there was a slight but statistically significant stimulation of eosinophil colony numbers. In contrast, incubation with high concentrations of dexamethasone, 3.3 X 10(-4) mol/L or 3.3 X 10(-6) mol/L, significantly reduced eosinophil colony numbers. Prednisone caused a significant reduction in plasma levels of Charcot-Leyden crystal protein but not of eosinophil granule major basic protein. The results indicate that soft agar assay of eosinophil colony growth by blood or bone marrow cells cannot be used to model the in vivo eosinopenic effect of glucocorticoids, levels of dexamethasone in excess of levels commonly administered in clinical practice are required to inhibit eosinophilopoiesis in vitro, and patients with peripheral blood eosinophilia may be more susceptible to the eosinopenic effects of glucocorticoids than normal subjects.

Blood Proteins↗
PubMed1986

Extracellular deposition of eosinophil granule major basic protein in lymph nodes of patients with Hodgkin's disease.

Lymph nodes from each of the four histologic types of Hodgkin's disease were examined for the presence of eosinophils and for eosinophil degranulation by immunofluorescent localization of eosinophil granule major basic protein (MBP). Eosinophil degranulation shown by MBP deposition outside of eosinophils was found in six of eight nodes from patients with nodular sclerosing disease and in two of eight nodes from patients with lymphocyte depletion-type disease. Three nodes of the mixed cellularity type, one node of the lymphocyte predominance type, and one lymph node of the lymphocyte depletion type showed one or two small foci of extracellular MBP deposition. Lymph nodes from patients without Hodgkin's disease showed no extracellular deposition of MBP. Large numbers of eosinophils were found in seven of eight nodes of the nodular sclerosing variant, but were less frequently seen among the other types of Hodgkin's disease. The presence of extracellular MBP in lymph nodes of patients with Hodgkin's disease indicates that eosinophil degranulation commonly occurs and suggests that the released eosinophil granule proteins may participate in the inflammatory reaction in this disorder more extensively than is presently appreciated.

Blood Proteins↗
PubMed1986

Severe generalized reactions to ibuprofen: report of a case.

A 46-year-old asplenic, nonatopic woman experienced at least one severe generalized reaction to ibuprofen. During her initial hospitalization for suspected septic shock, several laboratory results suggested disseminated intravascular coagulation. Results of oral dye, preservative, and aspirin challenges and tests for systemic lupus erythematosus were negative. She had remained well since she stopped taking ibuprofen. Awareness of the possibility of severe reactions to ibuprofen should be maintained when this medication is prescribed.

Diagnosis, Differential↗
PubMed1984

Localization of a molecule immunochemically similar to eosinophil major basic protein in human placenta.

We have recently reported that human pregnancy is characterized by a 10- to 20-fold elevation of eosinophil major basic protein (MBP) immunoreactivity in maternal blood. Here we show, by immunofluorescence, that placental tissue specifically binds antibody to MBP in and around the placental X cells and placental-site giant cells and, using thin plastic sections, that placenta has no infiltrating eosinophils. The X cells line the inner aspects of placental septal cysts, and the cyst fluid, obtained by aspiration, contains immunoreactive MBP at concentrations of 100 micrograms/ml, a sixfold greater concentration than the highest levels measured in maternal blood. The soluble MBP immunoreactivities in placental homogenates and in maternal serum chromatograph identically on Sephadex G-50, and both these gestational MBP molecules migrate as though substantially larger than the MBP found in serum from patients with hypereosinophilic syndrome or purified from the eosinophil granule. Our inability to demonstrate eosinophils in maternal blood or placental tissue, coupled with the large quantities of immunoreactive MBP highly localized in placental cysts and the chromatographic behavior of this molecule, suggest that the MBP detected in human gestation is produced by placenta.

Animals↗
PubMed1984

Evidence for secretion of human eosinophil granule major basic protein and Charcot-Leyden crystal protein during eosinophil maturation.

Prior electron microscopic studies have suggested that immature eosinophils degranulate during normal maturation in human bone marrow. This hypothesis was tested by measuring levels of eosinophil granule major basic protein (MBP) and Charcot-Leyden crystal (CLC) protein in bone marrow sinusoidal blood. MBP and CLC protein levels were elevated initially in bone marrow sinusoidal blood from normal volunteers when compared with peripheral blood, and levels of both proteins decreased during serial sampling; CLC protein levels remained significantly elevated, while MBP levels declined to equal those of peripheral blood. To investigate whether MBP and CLC protein were secreted during eosinophil maturation, bone marrow cells were cultured in soft agar; MBP and CLC protein levels were measured in culture supernatants by RIA. There was a significant positive correlation between eosinophil colony growth and levels of each protein. Electron micrographs of cells in soft agar colonies provided ultrastructural evidence for secretion of granule products by immature eosinophils. These results support prior observations that eosinophil promyelocytes degranulate during maturation.

Adult↗
PubMed1983

Elevated serum levels in human pregnancy of a molecule immunochemically similar to eosinophil granule major basic protein.

We have shown that serum levels of a molecule immunochemically similar to eosinophil granule major basic protein (MBP) are elevated in pregnant women throughout gestation. MBP levels increase during gestation and plateau at approximately 7,500 ng/ml by the 20th wk (greater than 10-fold above normal). Levels return to normal after delivery, with a T1/2 of 13.7 d. The MBP in pregnancy serum is remarkably similar to the eosinophil granule MBP in that: (a) pregnancy MBP fully inhibits the binding of radiolabeled MBP standard in a double antibody radioimmunoassay; (b) this inhibition reaction is specific for human MBP because pregnancy serum produces no inhibition of the binding of radiolabeled guinea pig MBP in the guinea pig MBP radioimmunoassay; (c) in a two-site immunoradiometric assay for MBP, slopes of dose-response curves for pregnancy serum, purified MBP, and serum from a patient with hypereosinophilic syndrome are identical, and maximal binding is comparable; (d) reduction and alkylation of pregnancy sera increases measured MBP 100-fold, as previously shown for eosinophil granule MBP in serum; and (e) the MBP in pregnancy serum demonstrates the same pattern of heat lability as has been previously reported for MBP. Four observations have raised the possibility that the eosinophil is not the source of the MBP in pregnancy serum: (a) no correlation between serum MBP level and peripheral blood eosinophil count exists in pregnant women, in contrast to previous studies of patients with eosinophilia; (b) levels of three other eosinophil-associated proteins are normal or low in pregnancy sera, whereas the serum levels of these proteins are elevated in patients with eosinophilia; (c) the slopes of dose-response curves for pregnancy sera and MBP standards differ in the double antibody radioimmunoassay; and (d) the molecule in pregnancy serum elutes from Sephadex G-50 columns at the void volume, while eosinophil granule MBP and the MBP in serum of patients with eosinophilia elute at a volume consistent with the previously established molecular weight of 9,300. These findings suggest that the MBP in pregnancy serum is derived from a source other than the eosinophil.

Animals↗
PubMed1983

Allergen-controlled study of intranasal immunotherapy for ragweed hay fever.

Previous studies of intranasal immunotherapy have not included control groups treated with an irrelevant allergen. In the present double-blind study, we tested the effectiveness of intranasal immunotherapy in 20 patients sensitive to both short ragweed (SRW) and orchard grass (OG). Patients sprayed increasing concentrations of either SRW (n = 11) or OG (n = 9) extract intranasally six times per day for 8 wk before the SRW pollination season. The effects of this treatment were determined by analysis of symptom score diaries and clinical examinations during the SRW pollination season. SRW-treated patients received cumulative AgE doses from 3 to 59 micrograms (mean 21); this mean dose was approximately sevenfold less than that used in a previous study from our laboratory. All patients reported immediate hay fever symptoms after use of the nasal spray. Five patients (four SRW- and one OG-treated) reported episodes of mild epistaxis during treatment; no other unexpected side effects were noted. During the treatment period, more SRW-treated patients showed signs of nasal obstruction and edematous nasal mucosa than OG-treated control patients (p less than 0.03). During the SRW pollination season, the SRW-treated patients reported lower mean weekly symptom scores than the OG-treated control patients, but the difference was not statistically significant. Supplemental antihistamine use was significantly higher (p less than 0.016) in the OG-treated control patients during the SRW pollination period. Subjective assessment of treatment efficacy by patients was similar in both treatment groups. We conclude that intranasal immunotherapy was of only marginal benefit in this study.

Administration, Intranasal↗
PubMed1982

Membrane marker characterization of the eosinophil colony-forming cell.

We investigated the membrane markers of the eosinophil colony-forming cell (EO-CFC). Eosinophil colonies were identified by their ability to show densely packed cell growth and by staining for cyanide-resistant peroxidase activity. Bone marrow cells were characterized prior to soft agar culture by one of two methods: (1) standard erythrocyte (E) and erythrocyte-antibody-complement (EAC) rosetting, or (2) by the human T- and B-cell surface markers, Leu 1 and HLA-DR, using the fluorescence-activated cell sorter. Eosinophil colonies developed mainly from the nonrosetting, null cell population. EO-CFC lacked the human T-cell marker Leu 1, but demonstrated the human B-cell marker, HLA-DR. EO-CFC were also present in peripheral blood and possessed similar properties to those in the bone marrow. The results indicate that EO-CFC are derived from the null lymphocyte cell population and possess HLA-DR markers.

Antibodies, Monoclonal↗
PubMed1981

Immunotherapy with short ragweed fraction A:D-glutamic acid:D-lysine polymer in ragweed hay fever.

We report the first human trial of immunotherapy employing the nonimmunogenic carrier, D-glutamic acid:D-lysine linked to short ragweed (SRW) fraction A (fraction A:D-GL). Twelve SRW-sensitive patients with no immunotherapy during the previous 19 yr received a 2-mo (7/79 to 9/79) course of fraction A:D-GL (average dose 49.5 mg, range 21 to 78 mg). We compared their symptom scores and serologic changes with two control groups of SRW-sensitive patients. Patients receiving fraction A:D-GL demonstrated at least a tenfold decrease in skin-test sensitivity to SRW and had statistically lower mean seasonal symptom scores (p less than 0.02) than untreated controls. Mean seasonal symptom scored did not differ statistically from those of control patients on year 4 of immunotherapy. In contrast to the expected suppression of IgE, we found that fraction A:D-GL stimulated both IgE and IgG responses to SRW and SRW-antigen E. These increases in IgE and IgG antibodies were significantly greater than in the control groups and appeared to be due largely to injection of fraction A:D-GL. Though fraction A:D-GL was generally well tolerated, we noted mild generalized urticaria in three patients, and large local reactions in five others. The difference between our results and the earlier results in mice may reside in the particular characteristics of this preparation of fraction A:D-GL.

Adult↗