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Biomedical subjects

C D Bloomfield

Publications and source records attributed to C D Bloomfield.

At least 181 records · Page 10Linked to original sources
PubMed1984

Liver irradiation in stage IIIA Hodgkin's disease patients with splenic involvement.

Curative treatment for Hodgkin's disease for patients who are pathology-staged IIIA, spleen-positive, consisted of total nodal irradiation (TNI) alone at the University of Minnesota Hospitals prior to 1975. This approach has been modified since 1975 to give low-dose irradiation to the liver in addition to TNI because of the high recurrence rate with TNI alone. Recurrence-free survival improved significantly when the liver was irradiated as compared to results with TNI alone (78% vs. 41% at 5 years, p = 0.004). The 5-year, overall survival was not significantly different in the two groups (90% vs. 80% at 5 years, p = 0.373). Various prognostic factors were examined. Patients who received liver treatment had statistically significant improvement in recurrence-free survival as compared to patients who did not receive liver treatment in the following categories: anatomic substage IIIA1, histologic classification of nodular sclerosis, male gender, age less than 40, number of primary sites, and extent of splenic disease. However, these factors failed to show clinical significance as prognostic factors. We conclude that TNI with low-dose liver irradiation should be used as the primary modality of treatment of Hodgkin's disease, pathology-staged IIIA patients. We conclude that chemotherapy should be reserved for recurrences in view of the excellent current results and the lesser risk from treatment, especially the risk of carcinogenesis.

Adolescent↗
PubMed1984

Monoclonal antibody MCS-2 as the marker of phorbol diester-induced myeloid differentiation in acute undifferentiated leukemia.

Leukemic cells from 32 cases of acute leukemia were cultured in vitro with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to study their differentiative potential. Three cases of acute undifferentiated leukemia (AUL) were studied intensively. We found that culturing of leukemic cells with TPA can induce changes in cell surface antigens. In particular, MCS-2, a "pan" granulocyte/monocyte marker, was inducible in vitro in AUL and in acute myelogenous leukemia, while it was not inducible in acute lymphoblastic leukemia. BA-2 (recognizing the Mr 24,000 protein) and TA-1 (recognizing the Mr 170,000 and Mr 95,000 proteins) were also inducible in cases of AUL, acute myelocytic leukemia, and acute monoblastic leukemia, although these antigens are not limited only to leukemias of the myelomonocytic lineage. Our studies also indicate that undifferentiated cells could be induced to nonspecific esterase and sometimes to chloroacetate esterase reactivity while losing terminal deoxynucleotidyl transferase. Morphological studies in these cases revealed cytological maturation following TPA treatment. In most cases, these changes were also partially inducible by culturing cells in medium alone or with the addition of dimethyl sulfoxide but not to the extent that was demonstrated by TPA. Our studies showed that MCS-2 is a very good, specific marker of acute nonlymphocytic leukemia. A potential use for TPA to aid in the subclassification of patients with AUL is also suggested.

Acute Disease↗
PubMed1984

Glucocorticoid receptor levels predict response to treatment in human lymphoma.

Neoplastic tumor masses from 47 adults with B cell malignant lymphomas were examined for glucocorticoid receptors and in vitro sensitivity to glucocorticoids. The patients were then treated with dexamethasone as a single agent for 5-14 days. Forty-seven percent of patients achieved at least a partial remission; 40% had no significant tumor response. Lymphoma cells from patients who responded had significantly more glucocorticoid receptor sites per cell and greater in vitro sensitivity as measured by glucocorticoid inhibition of incorporation of thymidine than did tumor cells from non-responders. Using a receptor level of 3000 sites/cell, response could accurately be predicted in 82% of patients. Our data suggest that study of tumor glucocorticoid receptors and glucocorticoid sensitivity in vitro may allow selection of those patients with lymphoma who should receive glucocorticoids as part of combination chemotherapy.

B-Lymphocytes↗
PubMed1984

Stabilization of labile glucocorticoid-receptor complexes from acute nonlymphocytic leukemia cells by a factor from chronic lymphocytic leukemia cells.

Glucocorticoid-receptor complexes in cytoplasm from normal lymphoid and leukemia cells incubated with glucocorticoid can be resolved into three different components, activated, nonactivated, and mero-receptor complexes, in relative amounts, dependent on the conditions to which the cells or cytosols are exposed. Recently, we reported that cytosols of acute nonlymphocytic leukemia (ANLL) cells contained high levels of mero-receptor complexes relative to those of chronic lymphocytic leukemia (CLL) or normal lymphoid cells. In the present study, we examined the cause for the lability of cytosolic complexes of ANLL cells. Mero-receptor accumulated rapidly in ANLL cytosols in a time-dependent fashion. The accumulation was most rapid in cytosols which contained activated receptor complexes, but it also occurred in cytosols containing only nonactivated receptor forms. Molybdate (20 mM) slowed but did not prevent the conversion to mero-receptor. Cytosols of ANLL specimens of the M4 French-American-British class (with monocytoid differentiation properties), in general, contained more stable complexes than did specimens of the M1 to M3 French-American-British classes (primarily myelocytic differentiation) suggesting that lability may in part be related to the state or direction of differentiation of the leukemic cells. In keeping with this hypothesis, cytosols of polymorphonuclear cells isolated from normal blood were much more labile than were those of monocytes. Mixing experiments with ANLL and CLL cells showed that the lability of ANLL complexes is not due simply to a higher content of proteolytic enzymes in these cells, because addition of ANLL cells or cytosols to CLL specimens did not result in increased mero-receptor. To the contrary, addition of CLL cells to ANLL specimens greatly stabilized the cytosolic complexes. These findings indicate the presence of an endogenous factor, present in CLL but lacking in ANLL cells, which is capable of stabilizing cytosolic complexes.

Acute Disease↗
PubMed1983

Covalent labeling of rat thymocyte and human lymphoid glucocorticoid receptor.

Lymphoid cells contain specific receptors for glucocorticoids. We have used [3H]dexamethasone-21-mesylate to label covalently glucocorticoid receptors in rat thymic lymphocytes and in neoplastic cells obtained from patients with acute lymphoblastic leukemia and malignant lymphoma. The covalently labeled glucocorticoid receptors were identified by polyacrylamide gel electrophoresis (in the presence of 0.1% sodium dodecyl sulfate). In cytosolic fractions prepared from rat thymic lymphocytes, [3H]-dexamethasone-21-mesylate labels a protein (Mr approximately equal to 95,000) which was identified as the glucocorticoid receptor by the following criteria: (a) labeling of this moiety is inhibited by treatment with a 100-fold molar excess of glucocorticoids, such as dexamethasone and triamcinolone acetonide; and (b) the covalently labeled Mr approximately equal to 95,000 protein is activated (by heating at 20 degrees for 30 min) to a form that binds to DNA-cellulose. When intact thymocytes are treated with [3H]dexamethasone-21-mesylate, an Mr approximately equal to 95,000 moiety is also labeled covalently. Approximately 35% of the glucocorticoid receptors can be labeled covalently when intact thymocytes are treated with 100 nM [3H]dexamethasone-21-mesylate for 30 min at 4 degrees. Neoplastic cells from acute lymphoblastic leukemia and malignant lymphoma were treated with [3H]dexamethasone-21-mesylate. In all samples, an Mr approximately equal to 95,000 moiety was labeled covalently; labeling was inhibited by excess glucocorticoid. Smaller moieties were also identified by competition experiments; these may represent proteolytic fragments of the Mr approximately equal to 95,000 receptor. Thus, in rat and human lymphoid cells, [3H]dexamethasone-21-mesylate can be used to label covalently the glucocorticoid receptor.

Affinity Labels↗
PubMed1983

Glucocorticoids and lymphocytes. III. Effects of glucocorticoid administration on lymphocyte glucocorticoid receptors.

To determine the effects of glucocorticoid administration on the number of measured lymphocyte glucocorticoid receptor sites and the duration of such effects, seven normal volunteers were studied. Glucocorticoid receptor levels of the lymphocytes circulating in the blood of each volunteer were determined. Glucocorticoid was then administered in a regimen of a total of four doses of dexamethasone 4 mg p.o. every 6 hr. Determinations of the number of receptors were performed at 6 hr and at various subsequent times after the end of dexamethasone administration. When compared to baseline receptor numbers, six volunteers showed a decrease in receptor number after glucocorticoid administration (median maximum decrease 2,046 sites/cell). The fall in receptor number occurred rapidly, reaching a nadir within 30 hr from the end of glucocorticoid administration. The return of receptor number to baseline was more gradual, requiring from 3 to as long as 17 days in one subject. Our results suggest that in order to accurately interpret glucocorticoid receptor numbers in human lymphoid cells, glucocorticoid should not have been administered for 3 wk prior to determinations of receptor levels.

Adult↗
PubMed1983

Partial deletion of the long arm of chromosome 16 and bone marrow eosinophilia in acute nonlymphocytic leukemia: a new association.

Recently, several specific chromosomal abnormalities have been associated with distinctive clinical and/or morphological subtypes of acute nonlymphocytic leukemia (ANLL). To further investigate the clinical utility of karyotype analysis in ANLL, we have examined G-banded metaphase chromosomes at diagnosis in 61 consecutive patients. Of the 60 patients who had adequate mitoses, 47 (78%) had a clonal chromosome abnormality. The sole karyotypic abnormality found in 5 patients was a del(16)(q22). The unique pretreatment characteristic of these 5 patients was marrow eosinophilia ranging from 8% to 54%. No other patient had more than 4% marrow eosinophils. Among the patients with eosinophilia, all had Auer rods, serum muramidase was elevated in the 4 tested, and 4 had hepatomegaly at presentation. Both patients who survived initial treatment remain in complete remission at 23+ and 33+ mo. The data suggest that we have identified a new cytogenetic-clinical subtype of ANLL defined by the del(16)(q22).

Adolescent↗
PubMed1983

Nonrandom chromosome abnormalities in lymphoma.

G-banded chromosomes were studied from involved lymph nodes or other tumor masses in 94 patients with malignant lymphoma. Clonal chromosome abnormalities were identified in 91 patients including all 81 B-lymphomas but only 6 of 9 T-lymphomas. Many recurring chromosome abnormalities were found. Most common numerical alterations involved gains of chromosomes 12 (19% of patients), 18 (13%), 7 (12%), and 21 (10%). Structural abnormalities, which were more frequent than numerical alterations, most commonly involved chromosome regions 14q (71% of patients), 18q (36%), 6q (31%), 1p (24%), and 8q (19%). Seven recurring translocations were identified, and all except one involved 14q32. The most frequent were t(14;18)(q32;q21) in 22 patients, t(8;14)(q24;q32) in 9 patients, and t(1;14)(q42;q32) in 3 patients. Deletions most frequently involved the long arm of chromosome 6 at band q21 (11 patients) or q23 (7 patients). The common recurring chromosome abnormalities were correlated with histology (International Working Formulation for Clinical Usage) and immunological phenotype. Four abnormalities were significantly associated with specific histologies. Eighteen (82%) patients with t(14;18)(q32;q21) were follicular. Similarly, 82% of patients with del(6)(q21) were large cell lymphomas. Lymphomas with trisomy 7 were either diffuse large cell or follicular, while patients with t(8;14)(q24;q32) were either diffuse large cell or small noncleaved cell. A significant association with immunological phenotype was seen for t(14;18) only. All patients were either B- or complement lymphomas, and the heavy chain(s) was more commonly gamma and less frequently delta mu than among the total B-lymphoma population. We conclude that essentially all lymphomas have cytogenetic abnormalities; further study is required to determine their significance. Particularly, it will be of interest to see if oncogenes are found in the regions of these chromosome abnormalities.

Adolescent↗
PubMed1983

Analysis of activated and nonactivated cytoplasmic glucocorticoid-receptor complexes from human leukemia cells by rapid DNA-diethylaminoethyl minicolumn chromatography.

Glucocorticoid-receptor complexes in cytoplasm from normal lymphoid cells incubated with [3H]dexamethasone can be resolved into three different components. Two of these correspond to the well-established activated and nonactivated forms, while the third appears similar to the mero-receptor complex first described by Sherman et al. (Fed. Proc., 37: 167-173, 1978). Based on their differential affinities for DNA- and DEAE-cellulose in buffers of low ionic strength (the activated complex binds to DNA- and DEAE-cellulose; the nonactivated complex binds to only DEAE-cellulose; the mero-receptor-like complex binds to neither), we have developed a rapid minicolumn chromatographic procedure for separating these forms, and have applied it to examine the relative proportion of different complexes in cytosols from cells of leukemia patients. All samples from nine patients with chronic lymphocytic leukemia contained these three complexes in proportions similar to those seen with normal lymphoid tissue. Cytosols from six of eight specimens from patients with acute nonlymphocytic leukemia contained a lower proportion of activated complexes and a higher proportion of mero-receptor-like complexes than cytosols from normal or chronic lymphocytic leukemia cells. Whether such differences in the properties of cytosolic complexes are due to degradation taking place after the cells are broken, and whether they can be correlated to in vivo therapeutic response, is not known, but studies are in progress to answer these questions. The minicolumn procedure described here offers a simple and reliable method for these purposes.

Adolescent↗
PubMed1982

Cyclophosphamide, doxorubicin, vincristine, and low-dose continuous infusion bleomycin in non-Hodgkin's lymphoma: Cancer and Leukemia Group B Study No. 7804.

Fifty-eight evaluable patients with non-Hodgkin's lymphoma were treated with a low dose, 120-hour continuous intravenous infusion of bleomycin in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone. Pharmacokinetic data, obtained in six patients, confirm that steady-state plasma concentrations of bleomycin can be attained even with the administration of 2 units/day of the drug. Neither clinical pulmonary toxicity nor subclinical pulmonary changes, as determined by serial measurement of the single breath carbon monoxide-diffusing capacity, were observed. Compared to similar chemotherapeutic programs utilizing bolus administration of bleomycin, pulmonary toxicity may be reduced. Response frequencies among 37 previously untreated patients were similar to those obtained using the same chemotherapeutic agents but with intravenous bolus administration of bleomycin. In addition, 18 of 21 patients who had received prior chemotherapy responded. Low dose, continuous intravenous infusion of bleomycin may improve the therapeutic index of combination chemotherapy programs for non-Hodgkin's lymphoma.

Adult↗
PubMed1982

15;17 Translocation in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a relatively rare subtype of leukemia that has been reported to be associated with a specific chromosome abnormality, t(15;17). It has been suggested that this translocation may have a geographical distribution and its presence may signify a poorer prognosis. In this present series of 14 patients with APL, 9 patients (64%) had the t(15;17) and 5 did not; however, no significant differences in clinical features or outcome could be found between those who did and those who did not express the translocation. When ethnic backgrounds were explored, no differences were found. More cases of the t(15;17) were found in recent years (7 of 8 patients studied since 1978 compared to 2 of 6 before 1978). This corresponded to changes made in our cytogenetic techniques suggesting that the finding of the t(15;17) may be a function of technique, rather than a real difference in disease entities, and all patients with APL may have the t(15;17) when appropriately studied.

Adult↗
PubMed1982

Acute promyelocytic leukaemia: a study of 39 cases with identification of a hyperbasophilic microgranular variant.

Thirty-nine cases of acute promyelocytic leukaemia (APL) were divided into two morphological subgroups, typical hypergranular APL (31 cases) and microgranular APL (eight cases, 21%). The leukaemic cells in the microgranular APL cases were characterized by striking nuclear folding or lobulation; granulation was present in most of these cells but was less abundant and finer than in typical APL. In three microgranular APL cases a distinctive small leukaemic promyelocyte with unusual nuclear lobulation and deeply basophilic cytoplasm containing few or no visable granules was the predominant leukaemic cell. This small hyperbasophilic promyelocyte was also present as a minor population of cells in the other five microgranular APL case and in 28 of the 31 typical APL cases. Ultrastructurally the most abundant promyelocytes in microgranular APL had smaller and usually fewer granules than in typical APL; other characteristic ultrastructural features of APL were found with equal frequency. The median blood leucocyte count was significantly higher in microgranular APL, 83.0 x 10(9) x 10(9)/l, than in typical APL, 1.8 x 10(9)/l (P less than 0.01). The median duration of complete remission (CR) for microgranular APL, 6.5 months, was shorter than the 21 + month median CR for typical APL. The morphological characteristics of microgranular APL may mimic those of myelomonocytic leukaemia; however, the presence of cells with multiple Auer rods, large inclusions of Auer-like material and the small hyperbasophilic promyelocytes are important distinguishing features. In equivocal cases cytochemistry, electron microscopy and cytogenetic studies may verify the diagnosis.

Adolescent↗
PubMed1982

5-azactidine and zorubicin for patients with previously treated acute nonlymphocytic leukemia: a Cancer and Leukemia Group B pilot study.

Twenty-nine adults with advanced acute nonlymphocytic leukemia were treated with an intensive chemotherapy program consisting of 5-azacitidine and zorubicin. Overall, eight patients (28%) achieved a complete remission. Although only one of 19 patients with refractory leukemia responded, seven of ten patients who were treated immediately following relapse from a prior remission achieved another complete remission. The duration of remission ranged from 5 to 33 weeks (median, 14). Treatment resulted in severe toxic reactions including myelosuppression, renal tubular dysfunction, and elevations in liver enzymes. In addition, each of the 15 patients who died of treatment-associated complications had a severe infection. This combination of 5-azacitidine and zorubicin is relatively ineffective for truly refractory leukemia, but it may be a useful alternative following relapse.

Acute Disease↗