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Biomedical subjects

D Dantchev

Publications and source records attributed to D Dantchev.

At least 37 records · Page 2Linked to original sources

Preliminary results of a phase II trial of aclacinomycin in acute leukaemia and lymphosarcoma. An oncostatic anthracyclin that is rarely cardiotoxic and induces no alopecia.

A phase II trial of which preliminary results are available for 22 patients indicates that aclacinomycin applied in a continuous modality induced complete and partial remission in four of nine patients with acute lymphoid leukaemia that was resistant to all previously available drugs, and in four of eight patients with stage V lymphosarcoma (leukaemic). Bone-marrow toxicity was the major side-effect. Only one patient of 20 suffered from cardiac toxicity; no one had alopoecia. This very low incidence of myocardial lesions and the absence of hair loss had been predicted, respectively, by our electron microscope study of the myocardium and the light electron microscope study of the skin of golden hamsters [7], a test that detects frequent severe myocardium and skin toxicities for adriamycin and some anthracyclin analogues such as detorubicin, which was found to be toxic in a high percentage of patients in a clinical trial conducted by the E.O.R.T.C. Clinical Screening Group [8].

Acute Disease↗

The effects of certain immunity systemic advuvants, PHA, and human gamma globulin on the thymic cortex of mice: a light and electron microscope study.

Thymus of (C57Bl/6 x DBA/2) F1 mice was examined histologically, histochemically and ultrastructurally, seven days after intravenous injection of BCG, pertussis vaccine, lipopolysaccharide or human gamma globulin, or intraperitoneal injection of complete or incomplete Freund's adjuvants or of phytohemagglutinin. Only BCG induced a marked increase of the secretory activity of the thymic epithelium at all histological sites (cortex, corticomedullary junction and medullar). Only with this adjuvant was the epithelial hyperplasia associated with marked mitotic activity and high percentage of cells with cytoplasmic pyroninophilia among cortical lymphoid cells. The other substances tested produced different changes in the thymic epithelial cells according to the histologic zones. These results suggest that the epithelial cells of the cortex, the corticomedullary junction and the medulla respond differently to the agents tested and that the action of these substances upon thymus-dependent lymphoid cells may be indirect perhaps involving factors secreted by the epithelial cells.

Adjuvants, Immunologic↗

Revised seminology of the different mononuclear cells under scanning electron microscopy.

Scanning electron microscopy shows that the thymus cell surface is not smooth but slightly undulated; this type of surface characteristic is found on the cells of several types of T-lymphocyte tumors such as T-cell lymphosarcoma, mycosis fungoides, and T-immunoblastic lymphosarcoma. The cell surface of Frabricius' bursa is covered with numerous short villi. They are found on the cells of several kinds of B-lymphocyte tumors, including B-cell chronic lymphoid leukemia, B-prolymphocytic lymphosarcoma, and B-immunoblastic lymphosarcoma. Mycosis fungoides cells frequently have a characteristic shape. Normal and myeloma plasma cells are similar in shape but their surface is covered with numberous characteristic tiny balls. Immunoblasts are twice the size of so-called small lymphocytes. In the blood and in the lymphocyte population transformed by mitogens, cell surfaces vary from completely smooth (with no undulations as in thymic cells) to villous, with short to very long villi. These variations are visible even when a constant technique and the critical-point drying method are used. Their significance, however, is not known.

Animals↗

Endogenous DNA polymerase of a transformation-defective rous sarcoma virus: characterization and comparison with the enzyme of the non-defective parent.

An RNA-directed DNA polymerase associated with transformation-defective (td) segregant of Rous sarcoma virus (RSV) has been characterized. The enzyme required both a monovalent and a divalent cation, a sulfhydryl reducing agent, and all four deoxyribonucleoside triphosphates for the expression of maximal activity. Sensitivity of the endogenous RNA-directed DNA polymerase activity to a low concentration of pancreatic RNase indicated that the enzyme utilized the td virus endogenous RNA as template. Maximal DNA synthesis was observed in a reaction mixture of pH 8 - 8.5 at 45 C with a manganese concentration of 1 mM. The enzyme of the td virus responded to exogenous template-primers in a manner characteristic of DNA polymerase of RNA tumor viruses, and the response became substantially greater when noncomplementary precursors were omitted from the reaction mixture. The endogenous reaction kinetics were examined. Three phases of DNA synthesis could be distinguished. Evidence was obtained showing that during the third and slowest phase of DNA synthesis the reaction mixture was not depleted of precursors and that the enzyme was fully active to initiate DNA synthesis with newly-added viral or synthetic RNA templates. Comparison of TMP and dAMP incorporation kinetics suggested that at the initial phase the enzyme preferentially copies A-rich region(s) of viral RNA. A comparison was also made between the endogenous reaction of the td virus and that of its parent sarcoma virus. The pH optimum, metal ion requirements, effect of sulfhydryl agents, response to exogenous template-primers, and kinetics of DNA synthesis, were all compared. No significant difference between the reaction of the td virus and its sarcomatogenous counterpart could be demonstrated.

Avian Sarcoma Viruses↗

Infectious viral DNA in Rous sarcoma virus-transformed nonproducer and producer animal cells.

Nonproducer and producer RSV-transformed cells and producer nontransforming virus-infected cells harbor viral DNA specifying the respective avian tumor virus. In nonproducer Rous sarcoma cells, the residing viral DNA is linear, double-stranded and covalently linked to the chromosomal DNA. Both double-stranded and single-stranded forms of RSV DNA transfect chicken cells. The progeny virus is indistinguishable from the DNA parent with respect to the morphological, biological and antigenic properties. Unlike the DNA extracted from nonproducer RSV-transformed mammalian cells, that extracted from producer RSV-transformed chicken cells gives rise, in transfection experiments, to both sarcoma virus and its nontransforming derivative. The DNA from nontransforming virus-infected chicken cells generates only nontransforming viruses. The frequency of nontransforming virus recovery is different from that of sarcoma virus recovery, the latter being a nonlinear function of the amount of transfecting DNA, while the former may suggest a linear relationship. On the other hand, the end-point dilution of transfecting DNA for sarcoma virus recovery is approximately the same as that for nontransforming virus recovery. The following is assumed: Sarcoma viruses and nontransforming derivatives are recovered from two different species of viral DNA which carry or lack, respectively, the transforming genetic material. The size of double-stranded viral DNA is substantially smaller than 20 times 10(6) daltons. In transfection experiments, the sarcoma virus DNA is first integrated into the host cell genome before being expressed, while the nontransforming viral DNA apparently bypasses the integration step. The latter DNA generates the progeny virus when taken up, carried, and transcribed in a permissive cell.

Animals↗

Infectivity of Rous sarcoma cell DNA: comparison of two techniques of transfection assay.

A DNA extracted from a clone of chicken cells transformed by the Schmidt-Ruppin strain of Rous sarcoma virus, subgroup D(SR-RSV-D), was assayed for infectivity by means of DEAE-dextran and calcium techniques. The calcium technique like the previously described DEAE-dextran procedure gave rise to viruses in transfection assays with both native and denatured (S1 nuclease susceptible) DNAs. The efficiency of these transfection techniques with native DNA was compared and found to be about the same provided that with the calcium technique carrier DNA was used to complement DNA concentrations lower than 2.5 mug/ml.

Animals↗

Immunoblastic lymphosarcoma, a cytological and clinical entity?

We have studied 20 cases of haematosarcomas belonging to lymphosarcomas (T or B-cell markers, absence of the reticulosarcoma characters in sections, on smears, with conventional and scanning electron microscopy). Their cells which appear as large pyroninophilic cells on sections, as large very basophilic cells with blastic nuclei and often cytoplasmic vacuoles on smears, as having many polyribosomes and usually no ergastoplasm with conventional electron microscopy, and as large cells of the lymphocytic series with scanning electron microscopy resemble the cells which we described in adenitis in 1955 (9) and in the graft-versus-host-reaction in 1961 (6), which Gowans (15) showed resulted from lymphocyte transformation, and which Dameshek (10) called immunoblasts. Many of these cases of immunoblastic lymphosarcoma (ILS) identified on their cytohistological characteristics [also recognized by Lukes et al. (24, 25) and Lennert et al. (21, 22)], present aetiological, clinical and pronostic characters which let us suppose that it may be not only a cytological entity but also a cytoclinical entity : a) it affects males in 85% or the subjects; eight patients came from mediterranean countries outside France; two patients had a history of chronic rheumatoid manifestations; b) the disease was at stage IV at the first presentation in 10 patients out of 20; it was revealed by profound (mediastinal or abdominal) localizations in 60% of cases (12 out of 20); it presented a hypoglobulinaemia in eight out of 13 patients; in six out of the 15 patients treated before leukaemic conversion, the chemotherapy usually efficient in lymphosarcoma (LS) failed to induce remission. This type of LS has a poorer prognosis than other types of LS (median for all stages : eight months). It led to the death either after its conversion to leukaemia (nine out of 20 cases), or by vital organ (as brain or kidney) infiltrations.

Diagnosis, Differential↗

Progress in the classification of lymphoid and/or monocytoid leukemias and of lympho and reticulosarcomas (non-Hodgkin's lymphomas).

New methods helpful in the classification of lymphoid and monocytoid leukaemias and haematosarcomas have recently become available. Among the most valuable procedures have been those detecting immunological markers and the ultrastructural analysis permitted by convention and scanning electron microscopy. The results of these studies, taken together with a meticulous morphologic examination on Giemsa smears allow a more subtle classification on these neoplasias. Among the most interesting points, one can list: a) The observation that all the prognostic parameters in the four types of common acute lymphoid leukaemia (ALL) (prolymphocytic, microlymphoblastic, macrolymphoblastic, prolymphoblastic) such as age, tumour mass (or leucocytosis) are related to the cytological type; T marker may be found in all these types, except in the prolymphoblastic; b) T or B acute lymphoid immunoblastic leukaemias has been described as a fifth type of ALL; c) The lymphosarcomas which can be histologically nodular (composed of B cells) or diffuse (composed of cells presenting B, T or no markers) can be cytologically prolymphocytic or lymphoblastic (or lymphoblastoid) if they are nodular, prolymphocytic, lymphoblastic or immunoblastic if they are diffuse; true (African) Burkitt's lymphosarcomas (BLS) must be distinguished from all the pseudo (non-African) Burkitt's lymphosarcomas which have been described elsewhere and which are either immunoblastic or lymphoblastic (oid) lymphosarcomas with a few macrophages. d) The diagnosis of reticulosarcoma which was in the past abusively carried out (because of confusion with immunoblastic lymphosarcoma) is based on the presence of many reticulins fibers at histological examination and on the cytological aspect of the cells on smears (the distinction of those cells with immunoblasts is easy).

Azure Stains↗