Induced leukemias and their connection with radiation exposure

The cytogenetic study of bone marrow cells was performed in 40 patients with secondary leukemias which have arisen after application of cytostatic and/or radiotherapy for primary tumours (Hodgkin's disease, lymphomas, acute lymphoblastic leukemias, breast cancer and other solid tumours). The comparative analysis of results has shown, that the leukemias after irradiating or application of alkylating agents and irradiation, have the quite particular clinico-morphological and cytogenetic characteristics. In 70% of cases these diseases develops as smouldering leukemias with subsequent transformation in M-4, M-6, and rarely M-2 cytochemical variants. Primary cytogenetic events in 60% of researched karyotypes are the losses of long arms or whole chromosomes 5 and 7. In 20% of the researched cases normal karyotype was found, in the left 20%, the changes of a karyotype not including anomalies 5 and 7 chromosomes were detected. The obtained outcomes allow to consider the discharged complex of tags as reference for leukemias, induced by irradiating or chemical agents with similar mechanism of action (alkylating agents, benzene and its derivates). This complex of tags is typical for induced leukemias, and in a combination with definition of a level of stable aberrations in peripheral blood lymphocytes, can be utilised for abjection of radiation-induced leukemias from common mass of cases detected in regions, polluted by radionuclides. In this study in 60% of cases only specific for secondary leukemias chromosomal aberrations, including monosomy 5 and 7, rearrangements of 11q23 were found. On the base of the obtained data the differences in concepts of "secondary" and "induced" leukemias are considered.     

AKR leukemogenesis: identification and biological significance of thymic lymphoma receptors for AKR retroviruses.

We have previously demonstrated that in vitro cell lines of mouse thymic lymphomas express surface receptors specific for the retrovirus that induced them. This study extends these observations to an analysis of receptor-bearing cells in the preleukemic and leukemic phases of spontaneous AKR thymic lymphomagenesis. AKR mice regularly begin expressing N-tropic retroviruses (as assayed on NIH fibroblasts by the XC plaque assay) in several tissues early in life; thymic lymphocytes also express these viruses, but are not autonomously transformed. Later thymic lymphomas emerge which are capable of metastasizing in the host of origin or transplanting leukemias into syngeneic hosts. Just prior to the appearance of thymic lymphomas, these mice also begin producing xenotropic retroviruses [as assayed in xenogeneic (For example, mink) fibroblasts], and concomitant with the appearance of the leukemias is the appearance of "recombinant" retroviruses which cause mink fibroblast foci (MCF); these viruses express elements of both N- and X-tropic virus envelopes and N-tropic viral gene products in their cores. Spontaneous AKR leukemias also produce other retroviruses which do not cause XC plaques or mink fibroblast foci; these are called SL viruses. The subject of this study was to test whether in vivo thymocytes in the preleukemic and leukemic periods also bear receptors specific for N-tropic, recombinant MCF and SL AKR retroviruses. We demonstrated that each spontaneous thymic lymphoma does bear receptors that bind viruses produced by the lymphomas and MCF-247 to a high degree and that bind N-ecotropic AKR retroviruses less well. Thymic lymphocytes predominating in the preleukemic period do not express detectable levels of receptors for either of the viruses. In some mice, receptor-positive cells co-exist with receptor-negative cells; only the receptor-positive cells are capable of transplanting leukemia to syngeneic hosts. We conclude that the presence of specific cell surface receptors for lymphoma cell-produced and recombinant AKR retroviruses is a marker for leukemia in these hosts.     

T-cell subsets in the murine thymus during chemically induced leukemogenesis

T cell leukemias were induced in BDF 1 mice by methylnitrosourea (MNU). The phenotype of the leukemic cells is Thy1.2 +, PNA-, TdT+, TL+ and heterogeneous with respect to Lyt-1 and Lyt-2. About 70% of the leukemias have elevated amounts of gp70. During latency period of at least 9 + 12 weeks an early reduction in the various thymic cells and the CFU-S is observed, with almost complete recovery. Later PNA+ cells are reduced. Hydrocortisone treatment delays or enhances leukemogenesis, dependent on the time interval between hydrocortisone and MNU. Some mice show elevated amounts of gp70 in their bone marrow 2--3 weeks after MNU. The problem of target cells in the bone marrow and the thymus is discussed.     

IL-18 polymorphisms in hepatitis B virus related liver disease

Interleukine-18 (IL-18) was originally called interferon (INF-γ) inducing factor and plays a critical dual role in Th1 polarization and viral clearance. We aimed to explore whether single-nucleotide promoter polymorphisms (SNPs) are associated with the outcome of hepatitis B virus (HBV) infection. 271 HBV infected patients were recruited in this study out of these 109 were spontaneously recovered and 162 were diagnosed to be having persistent HBV infection which includes 48 chronic hepatitis, 84 liver cirrhosis, 30 HCC cases and were compared with 280 healthy controls. IL-18 promoter genotyping was performed with sequence-specific primers. The results demonstrated the significant involvement of genotype AA at position -607 in healthy controls (38.6%) when compared to cases (26.0%) (OR = 0.54 (0.385–0.797)) and also associated with spontaneous clearance (37.6%) compared to persistent HBV infections (17.9%) (OR = 2.76 (1.582–4.832)). Whereas, genotype CC at position -607 in cases (18.0%) when compared to healthy controls (6.7%) (OR = 3.03 (1.734–5.303)) also associated with persistent HBV infections (24.1%) compared to spontaneous clearance (9.2%) (OR = 0.31 (0.151–0.67)). And genotype GC at position -137 in cases (49.5%) compared to healthy controls (38.5%) (OR = 1.55 (1.11–2.18)). Whereas, genotype GG at position -137 in healthy controls (56.8%) compared to cases (45.4%) (OR = 0.63 (0.451–0.885)). No significant difference at position -137 was observed between spontaneous clearance and persistent HBV infections. These polymorphisms of the IL-18 gene promoter region at position -607 and -137 could be associated with different outcomes of HBV infection. The people with allele A at position -607 may be protected against HBV infection; moreover AA genotype is associated with spontaneous clearance.     

Chromosome study in leukemic C57Bl mice]

Whereas the incidence of spontaneous leukemias is extremely low in the C57Bl mice, the exposure of young animals to fractionnated X-ray doses can induce up to 85% of lymphosarcomas. The i.p. injection to isologous mice of acellular extract of spleen or lymphnodes from such leukemic animals results in the apparition of reticulosarcoma in the treated animals. Most of them die within three to four months. Our cytological observations performed at different intervals of time after i.p. of RadLV failed to demonstrate the presence of numerical or structural chromosome aberration in the leukemic animals.     

Human chromosome polymorphism and disordered reproductive function. I. Routine chromosome variants]

Routine polymorphic variants of chromosomes of 58 married couples with reproductive failure (two or more spontaneous abortions, stillbirths and malformed children) and 48 control couples, having two or more normal children and no spontaneous abortions and stillbirths, were investigated by conventional staining technique. Extreme variants of chromosomes 1, 9, 16, 17, 13--15, 21--22 and Y were found in 17.2% of subjects with reproductive loss and in 15.6% of control individuals. No significant differences in frequencies of scored routine variants were noted between married couples with reproductive failure and couples with normal reproduction.     

Critical closing pressure in the fetal vessel of the human placenta in vitro. II. Compared effects of a beta adrenergic substance, Salbutamol, on the critical closing pressure and vascular resistance.

Salbutamol effects upon the fetal vessels of the human placenta were studied in vitro, comparing the changes induced upon the critical closing pressure (CCP) and viscous resistance (R). Four normal full-term placentas were used. In each of them, 4 cotyledonary areas were perfused, thus obtaining a total of 16 measurements for the observation of spontaneous variations (blank), by perfusion with Krebs solution, and the same amount for the variations due to Salbutamol. The concentration used was 10 microgram/ml, with a 4.25 ml/min flow. The relative effect of Salbutamol upon CCP was its decrease--30.4% against a relative spontaneous variation of --3.6%. The mean relative effect upon R was much lower, --9.4%. against a mean relative spontaneous variation of + 3.3%. The advantages of using CCP instead of R as a parameter of vascular contractility are discussed. Furthermore, Salbutamol is suggested to be useful in improving fetal placental circulation.     

An EcoRI restriction fragment length polymorphism (RFLP) in the human c-erb A locus

Summary An EcoR1 restriction fragment length polymorphism (RFLP) was detected in the 3 end of the locus of the c-erb-A proto-oncogene. The frequency of the rarer allele was around 3.0% in a normal population of 107 unrelated individuals. This frequency did not significantly differ in DNA samples from patients with breast tumors or acute leukemias.     

p53 (TRP53) deficiency-mediated antiapoptosis escape after 5 Gy X irradiation still induces stem cell leukemia in C3H/He mice: comparison between whole-body assay and bone marrow transplantation (BMT) assay

Mice exposed to a lethal dose of radiation were repopulated with heterozygous p53(+/-) (TRP53(+/-)) bone marrow cells and then exposed to doses of 1, 3 and 5 Gy 1 month later. This resulted in the transplanted bone marrow-specific diseases other than competitively induced nonhematopoietic neoplasms. Interestingly, the present study showed a high frequency of stem cell leukemia, i.e., leukemias characterized by a lack of differentiation due also to p53 deficiency, even after 5 Gy irradiation. The frequencies of stem cell leukemias (and those of total hematopoietic malignancies) were 16% (24%) at 1 Gy and 45% (75%) at 3 Gy. Furthermore, markedly high incidences of stem cell leukemias were observed at 5 Gy in p53(+/-) mice, i.e., 87% (100%) in the transplantation assay and 60% (83.3%) in the whole-body assay, whereas a conventional whole-body assay induced only 14% in wild-type mice. The high incidence of stem cell leukemias observed in this study using heterozygous p53-deficient mice agrees with results of a previous study of homozygous p53-deficient mice and is consistent with the high frequency of loss of heterozygosity in the p53 wild-type allele observed in leukemias. This suggests that the target cells for radiation-induced stem cell leukemias may be p53-deficient hematopoietic stem cells.     

Cancer mortality among adolescents and young adults: A historical cohort in a reference institution for cancer treatment in Santa Catarina/South of Brazil 2002–2013

ObjectiveTo identify factors associated with early mortality from cancer in adolescents and young adults in a reference institution for oncology treatment in Santa Catarina, Brazil.MethodsWe studied a retrospective cohort with an intentional sample of adolescents (ages 15–19) and young adults (ages 20–29) diagnosed with neoplasia. Secondary data were acquired from January 2002 to December 2013. Kaplan–Meier and Cox regression methods were used for survival analysis. Logistical analysis tested the association between early death (lower tertile between diagnosis and death, according to cancer type) and clinical or sociodemographic variables.ResultsWe included a total of 889 cases with an average age of 23, with similar gender distributions and a predominance of Caucasian ethnicity. Using the Cox framework of proportional risks adjusted for neoplasia types and gender, individuals with non-hematological neoplasia (solid tumors) presented a 47% higher risk of dying when compared with individuals diagnosed with leukemias and lymphomas (HR: 1.47; 95%CI: 1.12–1.93). Chances of death were 31% higher for males than for females (HR: 1.31; 95%CI: 1.02–1.69). When adjusting for type of neoplasia and age (15–24 and 25–29) the risk of death by cancer was 51% greater in individuals diagnosed with non-hematological neoplasia when compared with individuals diagnosed with leukemias and lymphomas (HR: 1.51; 95%CI: 1.15–1.99). The chance of death by cancer in patients under the age of 25 was 33% greater when compared to that in older patients between the ages of 25 and 29 (HR: 1.33; 95%CI: 1.04–1.75). In multiple regression analysis, factors associated with early mortality from cancer were the number of years in school (P = 0.011) and time between diagnosis and start of treatment (P < 0.001).ConclusionsThe sample studied with a longer period of time between diagnosis and the start of treatment (access to oncology therapy) and with fewer years in school showed that these factors had important roles in early death from cancer for the observed individuals. This must be considered when planning and identifying risk in young cancer patients in order to lower the impact of the disease on mortality for this age group.     

Karyotypes of spontaneous human abortuses and several aspects of their phenotypic presentation]

In all, 172 human spontaneous abortuses were examined: 75 cases from the 1st trimester of pregnancy (all were karyotyped), and 97 ones--from 2nd and 3rd trimesters (59 cases were karyotyped). 31 cases of chromosomal anomalies were revealed. The incidence of chromosomal anomalies among the 1st and 2--3rd trimesters of spontaneous abortuses was 40.0+/-7.5 and 1.0+1.0%, resp. The general incidence of chromosomal anomalies among this series of spontaneous abortuses was equal to 18.0+/-2.9%. The question of phenotypical manifestations of chromosomal aberrations in spontaneous abortuses is discussed. The influence of gene structure of aberrant chromosomes on phenotypes of abortuses is supposed.     

Flux cytometry of the cellular cycle of leukemic cells of the blood

The coordination of flux cytometry and of a techniques of leukoconcentration allowed to determine the cellular cycle of nucleated cells of circulating blood, without logs nor enrichment of cellular type on a definitive moment. The study of acute leukemias allow to conclude that: 1) it exists in peripheral blood a synthetic activity of ADN bound to the presence of leukemic or blastic cells; 2) this activity allows to appreciate the spontaneous variations of synthesis and the incidence of chemotherapy.     

Eficiencia de las unidades de agudos de geriatría frente al resto de servicios hospitalarios. Análisis de la casuística de 5 años ajustada por GRD

Introduction

Hospital occupancy rate by older patients is high, and it will be even higher in the future. Their hospital stay is usually longer, making it important for hospitals to develop structures with the best efficiency possible.

Identification and quantitation of human T-cell antigen by antisera purified from antibodies crossreacting with hemopoietic progenitors and other blood cells

Anti-T cell globulin (ATCG) prepared from antihuman thymocyte serum by absorption with kidney, cells from patients with chronic lymphatic leukemias, and several lymphoblastoid cell lines was shown to react specifically with human thymus-derived lymphocytes. While high activity against thymocytes and a T-lymphoblastoid cell line could be demonstrated, ATCG remained negative against several chronic lymphatic leukemias and B-lymphoblastoid cell lines. The ATCG was used in the cytotoxic test, electronmicroscopy, and immunoautoradiography for identification of T cells in thymus, tonsils, spleen, blood, bone marrow, lymphatic leukemias, and lymphoblastoid cell lines. A comparison of these results with the ability to form spontaneous SRBC-rosettes revealed remarkable deviations between both markers in leukemias. Absorption with human brain failed to remove specific activity of ATCG. Labeling experiments by immunoautoradiography and investigations by complement fixation permitted quantitation of relative T-cell antigen concentration on different cell populations. As further evidence for specificity it could be shown that ATCG was no longer toxic for hemopoietic progenitors, whereas unabsorbed globulin reduced the number of colonyforming cells considerably.Abbreviations ALL acute lymphatic leukemia - ATCG anti-human T cell globulin (absorbed) - ATG anti-human thymocyte globulin (not absorbed) - Bm-C bone marrow cells - CFA complete Freund's adjuvant - CLL chronic lymphatic leukemia - EBV Epstein-Barr virus - GPC' guinea pig complement - HBSS Hanks' balanced salt solution - Ig immunoglobulin - PBS phosphate buffered saline - Per-Ly peripheral blood lymphocytes (normal) - Spl-Ly spleen lymphocytes - SRBC sheep red blood cells - VBS veronal buffered saline - Thy-Ly thymus lymphocytes - Ton-Ly tonsil lymphocytes     

Glycolipid changes in murine myelogenous leukemias: neutral glycolipids as markers for specific populations of leukemias

We have studied the glycolipid composition of six different murine myelogenous leukemias as well as that of T-cell leukemias and normal spleen cells. Neutral and acidic lipid fractions were isolated by column chromatography on DEAE-Sephadex and analyzed by high-performance thin-layer chromatography (HPTLC) and an HPTLC overlay method. Murine myelogenous leukemias were found to contain globo- and ganglio-series neutral glycolipids, e.g., glucosylceramide (Glc-cer), lactosylceramide (Lac-cer), globotriaosylceramide (Gb3), globoside (Gb4), Forssman glycolipid (Gb5), and asialo-GM1 (GA1). Monoblastic leukemia cells contained increased proportions of Gb3, Gb4, Gb5, and GA1. Monocytic and myelomonocytic leukemia cells contained increased proportions of Glc-cer and Lac-cer. Especially, Glc-cer accounted for approximately 60% of the total neutral glycolipids in monocytic leukemia cells. Gb3 was the major neutral glycolipid in reticulum cell neoplasm type A, and it accounted for approximately 75% of the neutral glycolipids. GA1 was the major neutral glycolipid in myeloblastic and granulocytic leukemia cells as well as T-cell leukemias. Especially, granulocytic leukemia cells contained predominantly GA1, and it accounted for approximately 80% of the total neutral glycolipids. The pattern of gangliosides in myelogenous leukemias was more complex when compared with that of the neutral glycolipids; murine myelogenous leukemias contained at least 13 gangliosides, including such major gangliosides as GM1, GM1b containing N-acetyl neuraminic acid and N-glycolyl neuraminic acid, and Ga1NAc-GM1b. Alterations of glycolipid composition in murine myeloid leukemias may be associated with cellular differentiation and maturation, and therefore these characteristic glycolipid species may be regarded as markers for specific populations of leukemia cells.     

Hybrid leukemia among acute childhood leukemias]

Four children with the acute leukemia are presented. Their blasts shown the presence of 2 cellular lines markers. Coexistence of markers in the blasts was detected with the technique of double staining the blasts from the bone marrow with: alkaline phosphatase-anti-alkaline phosphatase, and peroxidase with the use of monoclonal antibodies series. Analysis of blasts phenotype with monoclonal antibodies confirm the occurrence of leukemias different from the normally programmed cellular line. Deviations of leukemic cells phenotype may be explained with the fact that leukemogenesis is not an absolute block of cells differentiation but combines maturation disorders and proliferation enabling expression normally absent antigens. It confirms the concept of line preservation and presentation of "earlier frozen" phenotype, and explains the occurrence of leukemias in which blasts present phenotype of one line which does not comply with cell differentiation pattern. Further genotypic studies are necessary to clarify pathogenesis and origin of such blasts. Consequently examination of the larger group of patients with hybrid leukemias will enable conclusions concerning prognostic value of such findings and necessity of introduction of the special therapies.     

Expression of immunological markers on leukemic cells before and after cryopreservation and thawing

We have studied the effects of cryopreservation on the viability and on the expression of surface antigens of acute leukemia cells. Marrow samples were obtained at initial diagnosis from 89 patients with acute myeloid leukemia (AML), acute undifferentiated leukemia (AUL), and acute lymphoid leukemia (ALL). In AML, the mean viability was greater than 90% in the types M1, M4, and M5 of the French-American-British classification, 79% in M2, and 3% in M3 types. The viability was 74% in AUL. In ALL, the viability was 95% for pre-B leukemias, but only 2% in T-cell leukemias. The expression of myeloid antigens was studied before and after freezing and thawing using three monoclonal antibodies (NHL30.5, against poorly differentiated granulocytic leukemias, VIMC6 against differentiated granulocytic leukemias and granulocytes; and UCHM1 or CRIS-6, against monocytic leukemias and monocytes). The percentage of cells stained by NHL30.5 and UCHM1 or CRIS-6 was very similar before and after cryopreservation. For VIMC6, the mean staining after cryopreservation was 60% of the initial one. In pre-B ALL, the stainings by anti common ALL antigen before and after cryopreservation were also very similar. We conclude that leukemic cryopreserved cells are suitable for immunologic studies. The recovery is, however, very low in promyelocytic AML and T-cell ALL.     

Oncogenes and human leukemias

Eukaryotic cells contain a family of genes termed "cellular oncogenes" or "proto-oncogenes," thought to regulate normal cell growth and development. In some circumstances, such as following transduction by retroviruses, activation of these genes causes tumors and leukemias in animals. Possible mechanisms of cellular oncogene activation include: 1) DNA point mutation, deletion or insertion, 2) gene amplification, 3) gene activation by internal rearrangement, chromosomal translocation or promoter insertion, 4) recombinative events resulting in the formation of novel chimeric genes, and others. In this review, we consider data which implicates cellular oncogene activation in the pathogenesis of leukemia in humans. We discuss possible mechanisms by which oncogene activation may induce leukemias, as well as potential diagnostic and therapeutic implications.     

Absorption ratio of treatment couch and effect on surface and build-up region doses

Aim

In this study, at different fields, energies and gantry angles, treatment couch and rails dose absorption ratio and treatment couch effect on surface and build-up region doses were examined.