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Biomedical subjects

A Riccardi

Publications and source records attributed to A Riccardi.

At least 145 records · Page 8Linked to original sources

Effect of vincristine on bone marrow cells of patients with multiple myeloma. A cytokinetic study.

The cytokinetic changes induced by Vincristine (VCR) on bone marrow erythroblasts, myeloid cells and neoplastic plasma cells have been studied in four patients with plasma cell malignancies using combined DNA cytofluorometry and in vitro tritiated thymidine cytoautoradiography. The changes observed 9 h after the administration of the drug were in accordance with its S-phase specificity. The magnitude of the stathmokinetic effect was in fact roughly proportional to the proliferative activity of the different cell lines, i.e., marked on the erythroblasts, less evident on the myeloid cells and still lower on the plasma cells. In this last cell population VCR has also blocked or partially impaired the DNA synthesis. Nine days after VCR, the plasma cells were recruited into the proliferative cycle while the regeneration of the hemopoietic cells was already exhausted. Repeated administrations of VCR spaced at about 9 day intervals are more and more effective on the plasma cell population, since the S place specificity of the drug against the recruited plasma cells is potentiated. On the contrary, the regeneration of the hemopoietic cells is protected by this time interval.

Autoradiography↗

Effect of vincristine on the bone marrow cells of patients with multiple myeloma: a cytomorphologic study.

The cytologic changes induced by vincristine (VCR) on the erythroblasts, the myeloid cells and the neoplastic plasma cells were studied on the bone marrow of 5 patients with plasma cell malignancies. Nine hours after the administration of the drug, the cytocidal effect on the 3 cell types was proportional to the magnitude of the stathmokinetic effect induced in them: marked on the erythroblasts (whose percentage incidence was sharply reduced), more modest on the myeloid cells, and still lower on the plasma cells. Nine days later the plasmocytomatous infiltrate was reduced as compared to before therapy, while the aliquot of hemopoietic cells was restored. At this time the mitotic index of plasma cells, but not that of the hemopoietic cells, was higher than before VCR administration. These findings suggest that the tumor mass reduction by VCR is followed by plasma cell recruitment, which is in progress 9 days after the drug administration. On the contrary, the regeneration of the hemopoietic cells has repopulated the bone marrow and is already exhausted in this lag time. It is hypothesized that VCR administrations given at about 9 day intervals are more and more effective on the recruited plasma cells, owing to the phase S-specificity of the drug. The regeneration of the hemopoietic cells is protected by this time interval.

Bone Marrow↗

A rapid cytofluorometric method for quantitative DNA determination on fixed smears.

A study has been made of the possibility of using propidium iodide (PI) for the cytofluorometric determination of DNA in fixed smears. A preliminary spectrofluorometric study made it possible to define the optimal conditions for the excitation wavelength and the intensity of the emitted fluorescence. The stoichiometry and specificity of the DNA-PI bond were studied in different materials and for different fixation procedures. In order to check whether RNA might interfere, it was extracted enzymatically from test preparations selectively. The data from such treated sections were not significantly different from those obtained by means of the fluorescent Feulgen reaction (Pararosaniline-SO2) on the same material. On the other hand, some of the advantages of the PI method are important: (a) the time required for making ready and staining the preparations is very short, and in any case is considerably shorter than the Feulgen method; (b) the high quantum yield of the DNA-PI complex induces very high fluorescence intensities, which can, therefore, be easily measured, even with low sensitivity instruments; (c) the spectral conditions are particularly favourable for excluding the inner filter effect from the measurement; (d) the photo-decomposition is considerably lower compared to that found in preparations stained by the conventional Feulgen method. The wide possibility of excitation (from the u.v. to the green), together with the limited extent of the emission band (which is mainly in the red) are also conditions that are particularly favourable for obtaining multi-parametric determinations simultaneously from the same cell.

DNA↗

Cytokinetic changes in the peripheral blood of leukemic patients during cytostatic therapy. V. Effect of VP 16 213 studied with flow cytofluorometry and cytoautoradiography.

The cytokinetic effects induced by VP 16 213 (50-60 mg/sqm/12 hrs for 10 doses) on the peripheral blood and bone marrow blasts of two patients with acute myelomonocytic leukemia have been studied using DNA flow cytofluorometry and in vitro tritiated thymidine cytoautoradiography. Besides a striking cytocidal effect, the drug induced cell synchronization in the G2 phase of the cell cycle as evidenced by the building up of tetraploid nuclei without an increase in mitotic figures. The synchronizing effect was greater in the bone marrow than in peripheral blood. In one patient, the removal of the G2 block was observed which paralleled an increase in proliferative activity. The usefulness of flow cytofluorometry for rapidly detecting the cytokinetic changes induced in acute leukemia blasts by cytostatic drugs is affirmed.

Autoradiography↗

Cytokinetic changes in the peripheral blood of leukemic patients during cytostatic therapy. VI. Effect of arabinosylcytosine.

Flow and conventional DNA-cytofluorometry and in vitro tritiated thymidine cytoautoradiography were employed in the study of the cytokinetic changes induced by Ara-c on the peripheral blood blast cells of six patients with acute non-lymphoblastic leukemias. Nine courses of therapy were studied, in 5 of which Ara-c was administered in low pulse doses (20-60 mg/sqm) repeated every 12 hrs and in the other 4 it was administered in continuous infusion (90-150 mg/sqm) lasting 24 hrs. Low repeated pulse doses have little cytocidal effect and increase the 2n-4n cell percentage and, less markedly, the LI, while the median grain count is reduced. Many U-like cells and accumulation of 3H-TdR labeled blasts in early S phase were observed during therapy. The continuous infusion of Ara-c induces striking cytoreduction and concomitantly decreases the 2n-4n percentage and LI. Progressive recovery of 2n-4n percentage and LI over pretreatment values was observed 24-48 hrs after stopping infusion in one case and was probably due to cell recruitment following tumor mass reduction. Our data agree with the literature, which is briefly reviewed, in that they indicate that Ara-c in a low intravenous pulse frequently dose synchronizes the blasts in S phase while higher doses of the drug are more often cytocidal in S phase and cell recruitment can follow cytoreduction.

Adult↗

Cytokinetic studies on circulating neoplastic cells of Hodgkin's disease.

In two patients with advanced Hodgkin's disease the DNA content, the mitotic index and the in vitro tritiated thymidine labeling index of the neoplastic cells found in peripheral blood, bone marrow and, in one case, in ascitic fluid have been determined. Cytologically the tumor cells were classified into three groups: atypical mononuclear cells, Hodgkin (H) cells and Reed-Sternberg (R-S) cells. Two populations with clearly different kinetic features were recognized. The first one was that of atypical mononuclear cells which exhibited diploid DNA content and proliferative activity of moderate degree: tetraploid cells were, however, observed more frequently than expected. The second population grouped together H and R-S cells, had tetraploid modal DNA content and very high proliferative activity. Hodgkin cells had tetraploid or slightly greater DNA content while R-S cells exhibited also DNA values as high as octoploid and sometimes greater. It can be postulated that by endomitosis some atypical mononuclear cells give origin to H cells and that these assume the monstrous features of R-S cells while increasing their DNA content during the DNA synthesis phase.

Adult↗

Correlation of cell kinetic findings with morphology of non-Hodgkin's malignant lymphomas.

Kinetic studies were carried out on 6 benign and 37 malignant lymph nodes from patients with non-Hodgkin's malignant lymphomas (ML). The labeling index, DNA content, and cell distribution through the cell cycle were analyzed in the ML, which were classified according to the Kiel classification. Approximately 90% of the ML studied showed a clear diploidy; the only cases of polyploidy were limited to some centroblastic-centrocytic ML with more than 30% malignant centroblasts and to be single centroblastic ML. The labeling indexes ranged from 0.05 to 33%. No correlation was found between the proliferative rate and the degree of ploidy, while a grading of labeling index was found in relation to the three main DNA distribution patterns observed (i.e., G1 peak, S accumulation, and bimodal distribution through the cell cycle). From a kinetic point of view, the most heterogeneous groups were the lymphoplasmacytoid (subtype polymorphous) and centroblastic-centrocytic ML, where the degree of proliferation increased as the mixture of cell type (relative to the former group) and the malignant centroblastic component (relative to the latter group) increased.

Adolescent↗