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Biomedical subjects

A Ost

Publications and source records attributed to A Ost.

At least 91 records · Page 5Linked to original sources

Haematological remission of leukaemic polymorphic immunocytoma following splenectomy. Case report with longitudinal immunological and cytogenetic studies.

A 56-year old man with a Rai stage IV B-cell chronic lymphocytic leukaemia (polymorphic immunocytoma according to the Kiel classification) of mu kappa-phenotype with a clonal chromosomal abnormality in cells from peripheral blood, bone marrow, and spleen is reported on. Following splenectomy (without further therapy) the blood lymphocytosis gradually decreased to normal and the patient entered a remission, assigned 42 months after splenectomy by immunological and cytogenetic studies that revealed no cells of clonal origin in blood or bone marrow. Utilizing cellular markers of clonality, we thus confirm that haematological remissions may follow splenectomy. A subsequently developed orbital lymphoma (without leukaemia) consisted of tumor cells derived from the initial leukaemia cell clone as indicated by their immune and cytogenetic phenotype. The case report is discussed in relation to previous reports on "spontaneous" remissions of lymphoid leukaemias.

Antigens, Neoplasm↗

Preoperative short-term radiotherapy in rectal carcinoma. A preliminary report of a prospective randomized study.

Between 1980 and 1983, 373 patients with clinically resectable rectal adenocarcinoma entered a prospective randomized study aimed to evaluate the effect of short-term preoperative radiotherapy. Protocol violations were identified in 21 instances. Of the remaining 352 patients, 182 were randomized to surgical treatment only (S-group). Immediately, before surgery, 170 patients were irradiated to the pelvic region with 25 Gy (2500 rad) during a 5-day period (RT-group). Of these patients, 59% underwent abdominoperineal excision, 38% anterior resection, and 3% laparotomy only. At surgery distant metastases were discovered in 32 patients (9%). There were no significant differences between the groups in the distribution of age, sex, operative methods, and tumor stage according to the original Dukes' classification. During the follow-up time, ranging between 6 months and 3 years, tumor recurrence occurred in 35 patients, 19 in the S-group and 16 in the RT-group. Fifteen patients in the S-group had pelvic recurrence compared to 10 patients in the RT-group. Distant metastases occurred in six and eight patients, respectively. Two patients in each group had both pelvic and distant recurrence. There was no correlation between tumor recurrence and type of operation. Median time interval from diagnosis to pelvic recurrence was 10 months in the S-group and 16 months in the RT-group. Postoperative complications in the form of wound sepsis were slightly more common in the RT-group. In summary, the applied treatment regimen, is well-tolerated and apparently does not affect the Dukes' stage of the tumor. Although there is no statistically significant difference, there is a trend of less pelvic recurrence in patients receiving preoperative radiotherapy.

Adenocarcinoma↗

Del(3)(p13) in B-prolymphocytic leukemia--a new nonrandom chromosomal aberration possibly related to the c-ras oncogene.

Cytogenetic analysis was performed on the leukemic cells from two patients with B-prolymphocytic leukemia. Both patients had del(3)(p13) chromosomal abnormality, as well as other clonal aberrations. Del(3p) was previously reported in one case of B-cell prolymphocytic leukemia, and is known to be a specific aberration in small-cell carcinoma of the lung. In B-cell prolymphocytic leukemia, as in other B-lymphocytic leukemias/lymphomas, the karyotype often involves chromosomes #3, #6, #11, and #12. All of these chromosomes are suggested sites for the c-ras oncogene family.

Aged↗

Low density lipoprotein receptor activity in human leukemic cells--relation to chromosome aberrations.

Chromosome analysis and low density lipoprotein (LDL) receptor activity of leukemic cells from 38 patients with acute non-lymphocytic leukemia were correlated. Clonal chromosome aberrations were found in 22 patients, and an extra chromosome 8 was found in 7 of them. LDL receptor activity was significantly higher in patients with an extra chromosome 8 than in patients with other abnormalities or a normal karyotype. Chromosome 8 may harbor genes of importance for the expression of the LDL receptor.

Adolescent↗

Immune phenotype and prognosis in chronic B-lymphocytic leukaemia and leukaemic immunocytoma.

Fifty-nine patients with a leukaemic B-lymphocytic malignancy ("CLL") were studied. According to the Kiel classification, 29 patients had chronic lymphocytic leukaemia (CLL) and 30 had immunocytoma (IC). Cell surface immunoglobulin staining showed mu heavy chain phenotype in 14 patients, mu in 35, gamma in 7; in cells from 3 patients the staining was too weak to permit identification. The light chain phenotype was kappa in 39 patients, lambda in 17, and unidentified in 3. The immunoglobulin isotypes differed between the diagnoses. The gamma chain phenotype was found only in IC patients (p less than 0.02), and more CLL than IC patients showed a lambda chain phenotype (p less than 0.04). Blood lymphocytes from IC patients contained more T cells than CLL cell samples (p less than 0.002). No prognostic difference was found between the CLL and IC group. Compared to the lambda phenotype, the kappa phenotype was associated with a poorer prognosis in the IC group, but with a better prognosis in the CLL group. IC patients with mu phenotype had a poorer prognosis than those with gamma phenotype. Low relative T cell numbers were associated with a poor survival (p less than 0.01).

Aged↗

Immune phenotype heterogeneity in AML.

Blood cells from 46 patients with acute myeloid leukaemia were studied for expression of various surface markers, defined by a panel of 12 monoclonal antibodies and the expression of Fc gamma receptors. Corresponding studies were done on normal bone marrow cells. Antibodies which bound to leukaemic cells in high frequencies were those which most frequently also bound to normal bone marrow cells. Immunophenotypic analysis revealed a marked antigenic heterogeneity in AML, also evident within single FAB subclasses. However, leukaemic cells of FAB subclass M1 significantly more often expressed HLA class I antigen than those of FAB subclass M5a, whereas Fc gamma receptors which were expressed only on a few cells in M5a, were increasingly frequent on leukaemic cells of M1-M2, M4, and M5b leukaemias. The frequency of cells reacting with the monoclonal antibody T50/12,11,2 was related to the complete remission rate of the patients. Patients with high frequencies of cells reacting with this antibody had a better complete remission rate than patients with fewer cells binding to this antibody. The immunophenotypic heterogeneity an AML may reflect a great biological variability of this disease. This variability may be of importance for the classification and treatment of AML.

Adult↗

Leukemic myeloblasts expressing lymphoid markers.

Out of 60 patients with acute myeloid leukemia not preceded by chronic myelocytic leukemia or any preleukemic phase, 7 had both lymphoid and myeloid markers. All patients expressed common acute lymphatic leukemia antigen (CALLA) in 20% or more of their leukemic cells, which also showed positive peroxidase reaction. In addition, 4 patients had Auer rods. Two additional patients had morphologically clear acute monocytic leukemia (FAB M5b) and cells expressing CALLA. In 4 of the 7 patients the sum of the percentages of peroxidase or Leu M1 + and CALLA-positive blast cells exceeded 100%, suggesting that at least some of the cells had both myeloid and lymphoid markers. Moreover, out of 3 patients where double staining with the CALLA antibody J5 and the myeloid marker Leu M1 was performed, 2 had both markers on the same cells.

Adult↗

Gastrin and somatostatin in plasma and gastric biopsy specimens in pernicious anemia.

Five patients with megaloblastic anemia due to deficiency of vitamin B12 and achlorhydria and six normal controls participated in the study. The patients with pernicious anemia (PA) had elevated plasma gastrin levels, as expected, and lower plasma somatostatin (SST) levels than the control patients. The amount of gastrin and SST in the antral mucosa did not differ in the two groups of patients. In the fundic mucosa, the patients with PA had increased tissue concentrations of both gastrin and SST as compared with the tissue concentrations in the controls. These findings of hormone tissue concentrations were correlated to the number of argyrophilic cells. Thus, in the antral mucosa the number of argyrophilic cells did not differ in patients with PA and in the controls. In the fundic mucosa, however, the number of argyrophilic cells was significantly elevated in patients with PA as compared with the controls.

Aged↗

Prognostic information from cytogenetic analysis in chronic B-lymphocytic leukemia and leukemic immunocytoma.

Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic lymphocytic leukemia (CLL), 29 had immunocytoma (IC), two had prolymphocytic leukemia, and one had centrocytic lymphoma; one was not subclassified. Cytogenetic studies after B cell mitogen stimulation showed that six patients had an extra chromosome 12 as the sole abnormality. Another ten patients had an extra chromosome 12 together with other abnormalities. One patient had dup(12). Fifteen patients showed clonal aberrations without +12. Eleven patients showed only normal metaphases, and 12 patients were not evaluated cytogenetically. The cytogenetic subgroup pattern did not distinguish between CLL and IC patients. There was no significant difference between the CLL and IC groups as regards clinical findings and prognosis. However, the cytogenetic typing proved to be of prognostic significance. Increasing numbers of chromosomal aberrations within the cell clone were significantly associated with a poorer prognosis, ie, with impairment of survival (P = .04) and therapy-free survival (P less than 10(-4]. Patients with complex karyotypes (at least clonal aberrations) showed the poorest survival (P = .007). Patients with +12 required treatment earlier than patients with a normal karyotype (P = .01) and patients with karyotypic changes other than +12 (P = .006). These latter differences were even more pronounced when only IC patients were considered (P = .005 and P = .002, respectively). A multivariate analysis revealed that +12 was as strong an indicator of poor survival as advanced Rai or Binet stages and a stronger predictor of therapy-demanding disease.

Adult↗

Antibody producing human-human hybridomas. II. Derivation and characterization of an antibody specific for human leukemia cells.

Human-human hybridoma technology was used to immortalize human B lymphocytes from patients with acute myeloid leukemia (AML) to study the antigenic repertoire of the humoral immune response against the patients' own leukemia cells and against leukemic cells from other patients. Nine fusions were done with lymphocytes from seven AML patients, and all with the human RH-L4 B lymphoma line as malignant fusion partner. A total of 305 Ig-producing hybrids were obtained. 26 reacted with cell surface components on AML cells, but 21 were found not to be specific for leukemia cells, when screened for reactivity against a panel of normal and malignant cells of both human and murine origin. Five hybridomas secreted Ig with high specificity for human leukemia cells, but only one hybridoma culture, aml-18, was stable in respect to Ig-production and growth upon repeated clonings and expansion in liquid cultures. A method was developed to grow human hybridomas as ascites tumors in nude mice, but the ascites fluid did not contain increased amount of antibody. The reactivity of the aml-18 antibody (gamma, kappa) was analyzed against samples of mononuclear cells from peripheral blood of 63 patients with leukemia and with cytologically verified leukemia cells in the blood. 22 of 54 AML samples reacted with aml-18. The reactivity pattern was not correlated to any categories of the French-American-British (FAB) classification; two of four ALL were positive. Moreover, a pronounced intratumoral antigenic heterogeneity in regard to aml-18 reactivity was seen and indicates a high degree of diversity in the immunological phenotype within individual AML cell populations. The study demonstrates that some patients with AML generate an immune response against their autologous malignant cells, and that the antigenic determinant in the case of aml-18 is also expressed specifically on leukemic cells from other patients.

Antibodies, Monoclonal↗

Prognostic significance of terminal transferase activity and glucocorticoid receptor levels in acute myeloid leukemia.

A retrospective study was undertaken to evaluate terminal transferase activity and glucocorticoid receptor content as predictors of prognosis in 52 adult patients with acute myeloid leukemia (AML). Eighteen patients who had detectable levels of TdT in their leukaemic cells (greater than or equal to 0.1 unit microgram-1 DNA), had a higher complete remission rate than patients with low TdT activity. Patients below 60 years with increased TdT activity also had longer survival as compared to those with low TdT levels. By combining cytochemical analysis of peroxidase and immunocytochemical staining for TdT it was possible to show that the enzyme was located in leukaemic cells of myeloid origin. Leukemias of monocytic origin had no detectable TdT activity in 10/11 cases. The cellular content of the cytoplasmic glucocorticoid receptor varied from 0 to 2.8 fmol micrograms-1 DNA. There was no difference in receptor content between the different FAB subgroups. High levels of the receptor (greater than or equal to 0.22 fmol microgram-1 DNA) were positively correlated with the remission rate. Patients with TdT levels of greater than or equal to 0.1 unit microgram-1 DNA and a glucocorticoid receptor concentration of greater than or equal to 0.22 fmol microgram-1 DNA had significantly higher remission (P = 0.001) and survival rates (P = 0.007) compared with those with undectectable levels of both TdT and low receptor content. It is thus concluded that combined measurements of TdT and the glucocorticoid receptor are useful predictors of prognosis in AML.

Adult↗

Cytomegalovirus infection of human blood cells.

Isolates of human cytomegalovirus (CMV), passaged one to 10 times in vitro, regularly induced CMV early antigens (EAs) in human leukocytes. Most CMV EA-positive leukocytes were monocytes. A small proportion of the cells appeared to be polymorphonuclear cells or lymphocytes. EA-positive cells were detected as long as cells in the culture remained viable (seven to 13 days). There was no clear evidence of viral production during this period. In contrast, EA-positive leukocytes were only rarely found after exposure to the CMV laboratory strain Ad169, although this strain generally had a higher EA-inducing capacity than did isolates in human lung fibroblasts. CMV strain Ad169 may have been adapted to fibroblasts through the many in vitro passages in these cells, and the strain appears to be unsuitable for investigation of susceptibility to CMV.

Antigens, Viral↗

Acute leukaemia in a defined geographic area--incidence, clinical history and prognosis.

A consecutive series of patients (1978-1981) comprising all patients with acute leukaemia from a population of 475000 inhabitants was reviewed. Thus, 94 patients were diagnosed as having acute leukaemia. No patients were lost from follow-up. The incidence figures of ALL and AML differed significantly from those of Sweden as a whole. 9 patients were less than 15 years old. The median age of adult patients was 64 years, 60.8% being greater than or equal to 60 years old. Of adult patients with AML, 20% had a preleukaemic history (chronic myeloproliferative disorders, myelodysplastic syndromes and others). None of 6 patients with leukaemia as a metamorphosis of a chronic myeloproliferative disorder achieved a complete remission. The overall remission rate of the remaining adult patients was 25%. Treated patients, 15-39 years old, with AML without any preleukaemic history, had a complete remission rate of 80% compared to 12% for patients greater than or equal to 60 years old with the same diagnosis. Of 60 patients with 'primary' AML, 14 were not treated, mainly because of advanced age and complicating diseases. Most of these patients died within a week of admission.

Adolescent↗

Elevated low density lipoprotein receptor activity in leukemic cells with monocytic differentiation.

The receptor-mediated degradation of 125I-low density lipoprotein (LDL) was compared in normal white blood cells and leukemic cells. The cells were isolated from the peripheral blood and bone marrow of healthy subjects and patients with newly diagnosed leukemia. The cells from most of the 40 consecutive patients with acute myelogenous leukemia showed markedly higher degradation rates as compared to mononuclear cells and granulocytes from peripheral blood and nucleated cells from the bone marrow of healthy individuals. Leukemic cells from patients with monocytic (FAB-M5) or myelomonocytic leukemia (FAB-M4) exhibited the highest degradation rates. The rate of receptor-mediated degradation of 125I-LDL was also high in leukemic cells from all three patients with chronic myelogenous leukemia in blast crisis, as well as in two of three patients with acute undifferentiated leukemia. In contrast, leukemic cells isolated from two patients with acute lymphoblastic leukemia showed low rates. In most cases, there was little difference in LDL receptor activity between leukemic cells isolated from peripheral blood and those from bone marrow. Hypocholesterolemia was a frequent finding in the leukemic patients. There was an inverse correlation between the plasma cholesterol level and the rate of receptor-mediated degradation of 125I-LDL by the leukemic cells. Studies are now in progress to investigate the possibilities of using LDL as a carrier of cytotoxic drugs in the treatment of leukemia.

Acute Disease↗

Longitudinal studies of blood lymphocyte functions in non-Hodgkin's lymphoma.

The study comprises 26 patients with non-Hodgkin's lymphoma who entered complete remission. Lymphocyte subsets and spontaneous and mitogen (ConA, PWM)-induced DNA synthesis were recorded in purified blood lymphocytes harvested before treatment, in remission and in relapse. The T and B lymphocytopenia noted in untreated patients persisted in complete remission. At diagnosis the spontaneous DNA synthesis was increased and the response to mitogen was decreased as compared to controls. Both functions became normalised during complete remission in most patients under 60 yr. The lymphocyte abnormalities reappeared during relapse. A low response to mitogen (ConA) in complete remission seemed to predict early relapse in patients younger than 60 yr. It is concluded that functional abnormalities of blood lymphocytes in non-Hodgkin's lymphoma are closely related to the presence of active disease.

Adult↗

A study of the reproducibility of the diagnostic criteria for acute leukaemia.

The Leukaemia Group of Middle Sweden recently started a new multicentre study of treatment of adult patients with acute leukaemia from 6 centres. The criteria for the diagnosis, subclassification, degree of leukaemic bone marrow infiltration, remission and relapse are to be used by the morphologists of 6 different pathology departments. The reproducibility of the criteria has been studied by 3 of the morphologists concerned, in a retrospective review of a strictly consecutive series of 79 adult patients treated at Södersjukhuset, Stockholm, Sweden, in the years 1978 to 1981. The results show that the reproducibility of the criteria and the concordance of the morphologists when using them increased when the criteria were made more detailed and precise.

Acute Disease↗

Correlation of immunophenotype to morphology in unfavourable non-Hodgkin lymphoma.

The relationship between immunological markers and histology according to the Kiel classification was studied in 40 adult non-Hodgkin lymphoma patients of Rappaport unfavourable histology. The membrane-associated and cytoplasmic Ig as well as receptors for sheep erythrocytes, Fc gamma and C3d receptors were analyzed on cryostate sections and in suspension. In some cases, a more precise immunophenotype was achieved by the use of monoclonal antibodies detecting different T and B cell antigens. Eighty-eight per cent of the lymphomas had B-cell, five per cent T cell and 7 per cent non-B/non-T cell phenotypes. All CBCC and CC lymphomas expressed monotypic Ig, but only 66 per cent of the CB lymphomas. Thus, morphology alone did not consistently predict immunophenotype in large-cell lymphomas. A simultaneous expression of multiple heavy chains and cytoplasmic Ig was found in some lymphomas, suggesting an intratumoral differentiation. The nodular or irregular tissue distribution patterns for Ig and C3d receptors found in histologically diffuse follicle derived lymphomas also suggest intratumoral variations in the marker expression, probably related to differentiation. The results suggest that lymphoma immunophenotype is important in obtaining a definite diagnosis in large-cell lymphomas and that it may lead to a better understanding of the differentiation of lymphomas of low-grade malignancy.

Adult↗