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Biomedical subjects

F Frassoni

Publications and source records attributed to F Frassoni.

At least 199 records · Page 11Linked to original sources

Generation of CFU-C suppressor T cells in vitro. III. Failure of mitogen-primed T cells from patients with chronic granulocytic leukemia to inhibit the growth of normal CFU-C.

T lymphocytes were derived by E rosetting from the peripheral blood (PB) and bone marrow (BM) of 15 patients with chronic granulocytic leukemia (CGL) in the chronic phase of their disease. T cells were also obtained from 12 healthy individuals. T cells were incubated overnight either in culture medium (RPMI) or RPMI plus pokeweed mitogen (PWM). The supernatants were then recovered and the cells washed in fresh RPMI. T cells from normal donors and from CGL patients were then cocultured with normal allogeneic marrow cells grown in soft agar for CFU-C colony formation. Target marrow cells were also grown in agar in the presence of T-derived supernatants. The results of this study can be summarized as follows. (1) Normal PB and BM T cells efficiently suppressed autologous and allogeneic CFU-C growth after PWM stimulation. (2) T cells derived from peripheral blood or marrow of CGL patients failed to inhibit CFU-C growth, whether pretreated with PWM or not. (3) The supernatants of PWM-treated normal T cells strongly inhibited CFU-C colony formation, whereas the supernatants of PWM-treated CGL T cells had no CFU-C/suppressor activity. These data indicate that T cells from CGL patients cannot be primed to become CFU-C suppressor cells after PWM: stimulation in vitro and cannot release a soluble inhibitor of granulopoiesis produced by PWM-primed normal T cells.

Adolescent↗

Generation of CFU-c suppressor T cells in vitro. IV. effect of time on the inhibitory activity of mitogen-primed normal T lymphocytes.

Bone marrow and peripheral blood T cells were obtained from 15 normal individuals by E rosetting and cultured in round-bottomed microwells for 7 days in RPMI or in RPMI supplemented with mitogens (pokeweed mitogen, phytohemagglutinin or concanavalin A). Supernatants and cells were harvested on days 1, 2, 3, 4 and 7 and co-cultured with normal marrow cells in semi-solid agar to test their CFU-c suppressor activity. The results of this study indicate that (a) RPMI treated cells and their supernatants have no effect or an enhancing effect on CFU-c growth; (b) all 3 mitogens generate CFU-c suppressor T cells on day 1 of culture; (c) the inhibitory activity is detectable until day 4 of culture, though overall reduced, and is completely lost on day; 7 (d) the trend for supernatants of mitogen-treated T cells is quite similar with a tendency to complete loss of the inhibitory effect on day 7. We interpret these data as indicating that T cells release a soluble inhibitor of CFU-c growth within a few hours from polyclonal activation, the production of which is either controlled or lost with time in culture.

Anemia, Aplastic↗

Generation of CFUC suppressor T cells in vitro. II. Effect of PHA, PWM, and Con-A on bone marrow and peripheral blood lymphocytes from healthy donors.

T lymphocytes were derived by E-rosetting techniques from the peripheral blood and bone marrow of 12 healthy donors. Following incubation of 18 h with PWM, PHA, Con-A or culture medium (RPMI) alone, the lymphocytes were harvested by centrifugation and washed. Both lymphocytes and culture supernatants were tested for CFUC suppressor activity in semisolid bone marrow cultures. The results of this study indicate that (a) T cells and supernatants from unstimulated cultures contained no CFUC suppressor activity, (b) T cells and supernatants from cultures stimulated with PHA, PWM or Con-A significantly suppressed autologous and allogeneic bone marrow CFUC, (c) there was no significant difference between the ability of bone marrow or peripheral blood T cells to inhibit CFUC, and (d) mitogens alone had either no effect or a moderate enhancing activity on marrow CFUC. These findings suggest that generation of CFUC suppressor T cells occurs normally within a few hours of polyclonal T cell stimulation.

Bone Marrow Cells↗

Tobramycin versus gentamicin, in combination with cephalotin and carbenecillin, in patients undergoing bone marrow transplantation.

Thirty-six patients with severe aplastic anemia or acute leukemia undergoing bone marrow transplantation or intensive hematologic treatments were randomized to receive gentamicin (1 mg/kg/iv q8h) or tobramycin (1 mg/kg/iv q8h) in combination with carbenecillin (500 mg/kg/day i.v. in 4 doses) and cephalotin (200 mg/kg/day i.v. in 6 doses), at the onset of fever during granulocytopenia. Patients in the gentamicin group were treated for a total of 541 patient days (minimum 5, maximum 106), and patients in the tobramycin group for 426 patient days (minimum 9, maximum 48). All patients received oral decontamination, which included the amino glycoside (either gentamicin or tobramycin) given intravenously. This study showed that 1) no patient had an increase in creatinine level above 1.3 mg % and no patient developed renal failure, 2) there was no difference between gentamicin and tobramycin in the efficacy of treating febrile episodes and/or major infections, 3) prolonged intravenous administration (up to 48 consecutive days in the tobramycin group and 106 consecutive days in the gentamicin group) was well tolerated and effective in treating fever of unknown origin in granulocytopenic patients: 45 of 72 febrile episodes resolved while the patients had a granulocyte count below 500/mm3.

Adolescent↗

Erythropoiesis in myelofibrosis with myeloid metaplasia: recognition of different classes of patients by erythrokinetics.

A quantitative assessment of erythropoiesis was performed by means of a mathematical model of iron kinetics in 26 patients with myelofibrosis with myeloid metaplasia (MMM). A direct relationship between total erythropoiesis and red cell volume was revealed. This 'inverse' characteristic of erythropoietic control was the best marker of the proliferative nature of the disease. Three classes of patients were singled out by means of a cluster analysis of the erythrokinetic parameters. In class I (11 patients) the red cell volume was above the predicted normal in all but two patients. Erythropoiesis was sustained at 5--10 times the normal levels with a high degree of ineffective erythropoiesis. A fairly constant absence of erythroid activity over the sacral marrow was demonstrated. In class II most of the 12 patients had a decreased red cell volume. Erythropoiesis was sustained at 2--4 times the normal level with a high degree of peripheral haemolysis. Erythroid activity was recognized over the sacral area in all but two patients. The three patients of class III showed a pattern of erythroid failure and had the worst prognosis. It is suggested that these classes represent separate disease forms of MMM.

Adult↗

A monoclonal antibody to antigens expressed on MLR-activated T cells inhibits granulocyte macrophage colony formation.

A monoclonal antibody specifically reactive with MLR-activated T cells (MLR2) was added to light density normal marrow cells, depleted of adherent cells and T lymphocytes, and plated in soft agar for granulocyte macrophage colony formation. Colonies from MLR2-treated marrow cells were reduced to less than 10% of expected growth. The inhibition was not complement dependent, did not require the continuous presence of MLR2 in culture, and could not be detected also when human placenta-conditioned medium was used in the place of leukocyte feeder layers as a source of colony-stimulating factor (CSF). Co-culture experiments with MLR2 treated and untreated marrow cells further excluded the possibility of an indirect effect of MLR2 on CFU-c via auxiliary cells. The results of this study suggest that myeloid progenitor cells express a lymphoid antigen that is absent on resting or activated B cells and on resting T cells, but is expressed on activated T cells.

Absorption↗

Role of purified erythropoietin in the amplification of the erythroid compartment.

A single dose of Myleran induced a prolonged depletion of multi-potential haemopoietic cells and of early erythroid precursors to levels between 2 and 6 of control. In these mice, a priming dose of highly purified erythropoietin (Epo) or of any of 3 Epo preparations from different sources, and having different specific activities, increased the magnitude of the response to a test dose of Epo by erythropoietin responsive cells (ERC) in the hypertransfused mouse assay. As significant feeding into the ERC compartment from the most immature cells is unlikely because of the depletion induced by the Myleran, it may be concluded that highly purified Epo, not contaminated with other biologically active molecules, has a dual effect on the ERC: it causes increased amplification besides inducing differentiation into cells with the capacity to synthesize haemoglobin.

Animals↗

The ultrastructural localization of factor VIII-antigen in human platelets, megakaryocytes and endothelial cells utilizing a ferritin-labelled antibody.

By means of electron microscopy combined with the use of monospecific anti-factor VIII-antigen (VIIIR:AG) antibodies conjugated to ferritin, the subcellular localization of VIIR:AG in platelets, megakaryocytes and in endothelial cells has been established. The reported results suggest the possibility that the megakaryocyte is able to synthesize VIIIR:AG and also to secrete it by means of a microcanalicular system similar to that present in the endothelial cell. Platelets may derive their VIIIR:AG content partly from the megakaryocyte and partly from the plasma.

Antigens↗

Normal and leukaemic haematopoiesis in bone marrow and peripheral blood of patients with chronic myeloid leukaemia.

In the majority of newly diagnosed patients with chronic myeloid leukaemia (CML), the bone marrow contains consistent numbers of normal Ph-negative surrogate stem cells (LTC-IC) which seem to decline rapidly with time. This is confirmed by mobilization studies showing that early after diagnosis is the optimal time to collect Ph-negative progenitor to be utilized for restoring Ph-negative haematopoiesis. In the marrow of the majority of CML patients at diagnosis Ph-positive LTC-IC are found at a lower frequency than Ph-negative LTC-IC and, unexpectedly, they do not show a tendency to increase with time as long as patients remain in chronic phase. Therefore, the decline of normal haematopoiesis does not seem related to a parallel increase in Ph-positive stem cells.

Blood Component Removal↗

CMV infections following allogeneic BMT: risk factors, early treatment and correlation with transplant related mortality.

BACKGROUND: The impact of early detection of CMV infections in allogeneic bone marrow transplantation (BMT) and of early treatment with ganciclovir is still uncertain. METHODS: 98 patients undergoing allogeneic BMT for hematologic malignancies (n = 91) or aplastic anemia (n = 7) were monitored weekly for the expression of the lower matrix protein pp65 of cytomegalovirus (CMV) on peripheral blood cells (PB) and urine sediments (U) as detected by C10 and C11 monoclonal antibodies (Clonab, Biotest) and immunoperoxidase. Bronchoalveolar lavage (BAL) cytospin preparations were also studied in patients with clinically documented interstitial pneumonia. Patients were considered to be infected with CMV if pp65 was detected in PB (n = 15) or BAL cells (n = 6), or in the presence of serum CMV-IgM with (n = 7) or without (n = 3) pp65-positive cells in urine sediments. RESULTS: The overall actuarial risk at 300 days of developing a CMV infection was 35%. CMV serum/status (IgG) pre-BMT of donor and/or recipient predicted the occurrence of CMV infections post-BMT: in neg/neg donor/recipient pairs (n = 17) the actuarial risk at 300 days was 0%, compared to 41% in pairs in which donor and/or recipient were CMV seropositive (n = 81) (p = 0.001). 24/31 patients were treated with ganciclovir (DHPG), and 17 survive. Mortality of patients treated early with DHPG on the basis of CMV antigenemia was 18% compared to 42% for untreated patients (p = 0.9). Pretransplant donor/recipient seropositivity accurately predicted transplant related mortality (TBM): 6% in neg/neg pairs vs 41% in all other combinations (p = 0.008). CONCLUSIONS: The risk of developing CMV infections post-BMT can be predicted by pre-transplant serostatus, diagnosed by monitoring the expression of pp65-protein and correlates with transplant related mortality. The latter appears to be reduced by early treatment with DHPG.

Actuarial Analysis↗