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D Milosević

Publications and source records attributed to D Milosević.

At least 19 recordsLinked to original sources

Potential diagnostic, prognostic and therapeutic implications of some new regulatory proteins in hematologic malignancies.

Multiple cell surface receptors play an important role in the biology of hematological malignant cells. Like already clustered monoclonal antibodies, the use of new markers of differentiation provide some new information about their structure and function. Here we consider the role of few selected regulatory proteins that are most frequently involved in the processes of activation, cell differentiation and proliferation of human hematological malignant cells. These molecules, being either lineage-restricted or multi-lineage cell activation ones, are involved in cell-cell and cell-matrix communications. They are involved in various leukocyte functions such as mobility, interaction with endothelium, and homing. Since physiologic cell growth involves not only cell division, but also programmed-cell death, we considered some apoptosis-regulatory molecules implicated in the clinical heterogeneity of hematological malignancies. The presence or absence of staining for these molecules is not only an important discriminatory immunophenotypic feature, but it appears useful also for prognosis and particularly in an experimental therapeutical setting. The prognostic significance of cell-expression of these molecules has not yet been clearly established, but it might be helpful in the evaluation of stability and progression of the disease.

Antigens, CD↗

Tc-99m DTPA renal scintigraphy using deconvolution analysis with six functional images of the mean time to evaluate acute pyelonephritis.

In 38 children with proved P-fimbriated Escherichia coli acute pyelonephritis, Tc-99m DTPA dynamic renal scintigraphy in the zoom mode using deconvolution analysis was performed, and the results were compared with those of Tc-99m DMSA scans. From the dynamic study, six functional images of the mean time were generated. Each functional image was analyzed separately to search for focal areas of increased mean time within the kidney contour, especially over the kidney parenchyma. Time-activity curves from these areas were generated and analyzed. Tc-99m DMSA scintigraphy showed generalized or focal decreased uptake in 32 (41.8%) kidneys, and deconvolution analysis of Tc-99m DTPA scintigraphy revealed pathologic renographic curves in 58 (77.6%) kidneys. Prolonged whole-kidney and normal renal parenchymal transit times (dilatation without obstruction) were found in 38 (50%) kidneys, whereas prolonged whole-kidney and renal parenchymal transit times (dilatation with obstruction) were observed in 20 (27.6%) kidneys. Separate analysis of each of the six functional images of the mean time showed focal areas of increased mean time in the kidney parenchyma of 11 kidneys. In five cases, time-activity curves from these areas showed a sharp increase of activity on the descending part of the curve, which might reflect the return of urine from the collecting system into kidney cortex (i.e., intrarenal reflux). These results showed that in a urinary tract with acute pyelonephritis, urodynamic changes may lead to obstructive nephropathy and intrarenal reflux. Tc-99m DTPA renal scintigraphy in the zoom mode using deconvolution analysis with six functional images of the mean time has proved to be a valuable method to evaluate acute pyelonephritis, thus allowing dynamic and morphologic analysis of the urinary tract at the same time.

Child↗

The absence of correlation between immunoregulatory T cells and induced lymphoproliferative response in treated B-chronic lymphocytic leukemia patients.

BACKGROUND: Many data suggest T cell functional impairment in B-cell chronic lymphocytic leukemia (B-CLL). The mechanism responsible for this phenomenon is still unresolved. METHODS: In 88 B-CLL patients (RAI II-IV) the relationship between immunoregulatory T cells and PHA induced lymphoproliferative response (LPR) was analysed before and after the therapy. The number of peripheral blood CD3+, CD4+ and CD8+ T lymphocytes was determined by indirect immunofluorescence assay using monoclonal antibodies. LPR was estimated in whole blood culture method. RESULTS: The absolute number of CD3+, CD4+ and CD8+ cells in untreated CLL patients was much higher than in healthy controls (n = 26), but the percentages of these subpopulations, CD4/CD8 ratio and LPR to PHA were significantly (p < 0.00001) decreased. The chemotherapy induced a significant rise of CD3+ and CD4+ percentages (p < 0.006 < p < 0.022 respectively) in comparison to baseline levels, but their levels remained significantly (p < 0.00001) lower than the controls. The CD4/CD8 ratio was also elevated after the therapy (p < 0.048) but remained below the normal value as well. The absolute number of CD3+ and CD4+ T cells were normalized after treatment, while the CD8+ cells were still higher (p < 0.044) than controls. The increase of LPR has been registered after treatment, but it failed to reach the control values. We could not find any correlation between the number of immunoregulatory T cells and induced LPR (r = 0.07, for CD4+; r = 0.09 for CD8+ cells). CONCLUSIONS: These data indicate some profound lymphoid cell defect in CLL patients affecting CD8+ proliferation as well as LPR.

Adolescent↗

Lyophilized whole human melanoma cells stimulate human PBMC proliferation and enhance suppressive action of PBMC toward survival of the same malignant cell line in vitro.

The goal of this work was to determine: a) do lyophilized human melanoma BG or Fem-X cells affect the proliferative capacity of normal human peripheral blood mononuclear cells (PBMC) and b) does the PBMC six-days preincubation in nutrient medium with FBS with, or without lyophilized human melanoma BG or Fem-x cells, affect their suppressive action on the survival of the same malignant cell line in vitro. In the aim to avoid any stimulating effect of FBS, other group of experiments were done in nutrient medium with human AB serum in order to determine: c) does the PBMC six-day-preincubation with lyophilized human melanoma BG or Fem-x cells affect their antiproliferative action on the corresponding malignant cell line in vitro and d) does the PBMC six-day preincubation with lyophilized normal PBMC, obtained from healthy volunteer (as a source of allogenous, but not of tumor antigens), affect their suppressive action on the survival of both melanoma BG and Fern-x cell lines in vitro. Results obtained in the presence of FBS in nutrient medium, showed that lyophilized BG cells induced a proliferation of the healthy PBMC, depending on the number of stimulating lyophilized cells. Lyophilized Fem-x cells induced healthy PBMC proliferation in lesser degree than lyophilized BG cells. This stimulation was almost constant, not dependent on the number of stimulating lyophilized Fem-x cells. Six-day stimulation in vitro by both lyophilized melanoma cells enhanced the suppressive action of PBMC on the survival of the corresponding malignant cell line. Experiments done in nutrient medium with normal human AB serum showed that six-day stimulation with lyophilized melanoma cells enhanced, again, the suppressive action of PBMC on the survival of the corresponding malignant cell line. Contrary, six day preincubation of normal PBMC with the lyophilized healthy PBMC (obtained from other healthy person) inhibited their suppressive action on the survival of both malignant cell lines in vitro.

Adult↗

Effect of T-activin therapy on indomethacin modulation of lymphoproliferative response in vitro of melanoma patients.

BACKGROUND: Several studies showed that PGE-mediated immunosuppression in cancer patients may be differentially affected by conventional oncologic therapy. METHODS: Since there is little evidence about the action of immunotherapy on this suppression mechanism, we investigated the effect of therapy with a thymic agent-T-activin, on in vitro modulation of lymphoproliferative response (LPR) by indomethacin. RESULTS: The results demonstrated that indomethacin added in vitro enhanced LPR in early stage melanoma patients before therapy. T-activin therapy as an adjunct to surgery improved this lymphocyte function; the post-therapy in vitro addition of indomethacin did not significantly affect mitogen response. However, in those patients whose LPR was insufficiently enhanced by immunotherapy (3/8), indomethacin had improved their lymphocyte response. In the control patient group treated by surgery alone, indomethacin significantly enhanced LPR in vitro six months after operation. Although obtained in a small number of patients, our results indicate that the enhancing effect of T-activin therapy on lymphoproliferative response may be, at least in part, due to the effect on PGE-mediated suppressor cell activity. CONCLUSIONS: Furthermore, post-therapy in vitro testing may indicate a possible usefulness of this drug combination in some of the early stage melanoma patients.

Adjuvants, Immunologic↗

Richter syndrome with emphasis on large-cell non-Hodgkin lymphoma in previously unrecognized subclinical chronic lymphocytic leukemia.

The authors report seven cases of Richter's syndrome, i.e. of large-cell non-Hodgkin's lymphoma (NHL) arising in association with chronic lymphocytic leukemia (CLL). Six patients had the recently recognized variant of this syndrome, occurring in patients with previously undiagnosed subclinical CLL. All patients were treated with aggressive chemotherapy and a complete response of large cell NHL was achieved in 4/7. A complete response of NHL was observed in 3 out of 6, and a partial response in 2/6 patients with simultaneous occurrence of subclinical CLL and large cell NHL (response rate 5/6). Our findings might suggest that patients with Richter syndrome occurring in previously undiagnosed subclinical CLL could represent a better prognostic group in the overall population of patients with large cell NHL transformation of CLL.

Aged↗

Clinical and immunologic effects of T-activin therapy in early stage melanoma patients.

We investigated the clinical and immunological effects of T-activin therapy in early stage melanoma patients. Several immune parameters (the number of T cells-E-RFC and CD3+, their subsets-CD4+ and CD8+, the number of CD38+ and CD16+ cells, and mitogen-induced lymphoproliferative response-LPR) were analyzed in relation to the clinical course of the disease in patients treated by T-activin in addition to the surgery (n = 8), and in control patients treated by the surgery alone (n = 9). Immunological tests were performed before therapy and one month after the last (6th) cycle of T-activin, i.e. six months after surgery in controls. The patients were followed-up from February 1991 to August 1995. Clinical evaluation showed that disease-free interval for observed period was similar in both groups of patients (17.5 and 13 months), while the survival time was longer in T-activin-treated patients than in controls (40 vs. 24 months), although this difference was not significant. The phenotyping analysis of peripheral blood lymphocytes showed no changes of the pretreatment values of total T cells and their subpopulations regardless the clinical course of the disease in both groups of patients. The number of NK cells (CD16+) was significantly increased after T-activin therapy, but this increase was not associated with clinical benefit, since it was seen in patients with the progression of the disease. In control patients, the initial number of CD16+ cells did not change significantly, irrespective of the clinical course. The lymphoproliferative response increased significantly in 4 out of 5 T-activin-treated patients with the progression of the disease, while a slight increase of this lymphocyte function was seen in 3 disease-free patients. In patients treated by surgery alone, especially those with disease progression, the LPR was significantly decreased six months after tumor excision. These findings, although obtained in small number of patients, suggest an immunomodulatory action of T-activin therapy in early stage melanoma patients, which did not correlate with the clinical course of the disease. On the other hand, an almost doubled survival time in T-activin-treated patients in comparison to the controls, may indicate a possible effect of T-activin therapy on some other immune functions not evaluated in this study. Further investigations in a larger number of patients is needed for assessment of the true effectiveness of such therapy.

Adjuvants, Immunologic↗

Reactivity of monoclonal antibodies OK-CLL (anti-CD5) with peripheral blood cells of patients with B cell lymphoproliferative disorders.

Reactivity of OK-CLL monoclonal antibodies that can identify CD5 antigen on peripheral blood mononuclear cells, was investigated in 172 patients with B cell chronic lymphocytic leukemia (B-CLL) in clinical stages RAI O-I and RAI II-IV and in patients with non-Hodgkin's lymphomas, classified according to the Working formulation into high and low grade histologic type. The OK-CLL reactivity with B-CLLs in the initial (RAI O-I), as well as in advanced stages of disease (RAI II-IV) was significantly higher than in controls. Peripheral blood cells of lymphoma patients, regardless of histological type, showed a much lower values of the CD5 positive population than chronic lymphocytic leukemia (CLL) patients, and a non significant discrepancy between the number of cells stained with anti-CD5 and those stained with other T cell markers. In spite of the showed considerable decrease of CD5 positive cells in CLL patients during therapy, elevated number of this population compared to normal individuals, after chemotherapy, was found. However, in lymphoma patients of both types of malignancies, CD5 positive population increased concomitantly with therapy. These results may suggest that analysis of CD5 antigen expression on peripheral blood cells of patients with B cell lymphoproliferative malignancies may have diagnostic, or, in correlation with some relevant clinical parameters, a potential predictive value in the treatment of those patients.

Adult↗

[Effect of interferon alpha on immunologic parameters in patients with carcinoma of the renal parenchyma].

A wide range of immunological abnormalities have been described in renal-cell carcinoma (RCC). The only constant one was the decrease of CD4/CD8 ratio, reversible following radical nephrectomy in the absence of metastases. Alpha-interferon was administered with variable benefit to patients with metastatic RCC. The aim of this study was to document whether the treatment of patients with metastatic RCC, with unpurified human alpha-interferon, induced any change in the number and functional properties of peripheral blood T lymphocytes and monocytes. Fifteen patients were included in the study; all were treated with IFN 2,000,000 IJ/24h x 15 days, with an intercycle interval of 15 days during at least 4 cycles. The immunological analyses included the percentage and absolute number of E-rosette forming cells, CD3+, CD4+, CD8+ and CD4/CD8 ratio as well as the percentage and absolute number of monocytes and their phagocytic index toward the yeast particles. The analyses were done before the treatment and after the 4th cycle of the IFN therapy and compared toward the same analyses done in 22 healthy controls. Following IFN treatment two significant changes were noted: a decrease in CD4/CD8 ratio (mean 1.050 fall for 19% to 44%, mean 27.25% from the initial value) as well as a marked decrease in monocyte phagocytic index (p < 0.005). These data point to either disease-related or treatment-related decrease in the phagocytic properties of monocytes and the decrease of CD4/CD8 ratio.

CD4-CD8 Ratio↗

[Giant osteomas of the paranasal sinuses].

At the Otorhinolaryngologic Department in Novi Sad we investigated osteomas of the paranasal cavities registered from 1960 to 1989. The total number of the treated patients was 30, aged from 31 to 60 years. A special attention is given to a female patient, aged 65 years with osteoma covering two thirds of the right nostril, both ethmoids and right retrobulbar space. It progressed upwards to the base of the skull causing denudation of the dura mater at the surface of 2.5 x 1.5 cm, and consecutive liquorrhea. The removed tumor weighed 110 grams and belonged to giant osteomas of the paranasal cavities.

Adolescent↗

[Determination of T lymphocyte subpopulations in malignant lymphoproliferative diseases].

The aim of this work was to investigate T cell subset composition of peripheral blood cells in patients with acute myeloid leukaemia, acute lymphoblastic and chronic lymphocytic leukaemia, by enumerating T cells positive for receptors for sheep erythrocytes (E-RFC, A-RFC) using the method of E-rosette, and for CD3, CD4 and CD8 antigens, by indirect immunofluorescence technique, using the monoclonal antibodies of the OK series. The study was performed on 57 patients without therapy and 46 healthy persons. The results of enumeration of T cells and their subsets obtained in the stage of the disease when the total leukocyte count was below 20 x 10(9)/L, were markedly decreased in all three types of leukaemias. The most significant decrease of relative count of T cells and their subpopulations was obtained in CLL patients. Analysis of T cells subsets and their ratio in CLL patient in the stage of disease when the total leukocyte count as higher than 20 x 10(9)/L, demonstrated the most pronounced decrease of total T lymphocytes and CD4+ cells. The relative count of the "active" (A-RFC)T cells and CD8+ cells did not change, and was the same as in the patients suffering from CLL with a lower leukocyte count.

Humans↗

Lymphocyte reactivity in Imuran-treated guinea-pigs and in vitro effect of colchicine.

Imuran treatment significantly diminished macrophage migration inhibition in immunized guinea-pigs and the percentage of E-rosette forming cells in all treated animals. 10(-6) M colchicine in vitro significantly increased the percentage of E-rosette forming cells in Imuran-treated animals. The results suggest possible alteration of the lymphocyte receptors after treatment with Imuran.

Animals↗

Extraosseous osteosarcoma - two cases.

Two patients with extraosseous osteosarcoma of the gluteal region are presented. In one early case liquifaction of the tumour delayed the diagnosis due to confusion with a cold abscess. In the second patient the tumour developed in a region that had been subjected to post-operative radiotherapy for a uterine carcinoma seven years earlier. In both patients the tumour developed rapidly and with a fatal outcome only a few months after apparently satisfactory local excision.

Buttocks↗