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Biomedical subjects

M Repetto

Publications and source records attributed to M Repetto.

At least 109 records · Page 6Linked to original sources
PubMed1985

In vitro tests in severe aplastic anaemia (SAA): a prospective study in 46 patients treated with immunosuppression.

Forty-six patients with severe aplastic anaemia (SAA) were studied for CFU-c growth on admission and 1 month post-treatment with immunosuppression (IS). Twenty-three patients became transfusion independent after IS, and were considered responders, and 23 did not. CFU-c growth from unfractionated bone marrow cells was comparable in both groups on admission and 1 month post-treatment. CFU-c growth from E rosette depleted BM cells (E-BM) was also comparable on admission. However, 1 month post-treatment, responders showed a significantly higher CFU-c growth (P = 0.02) from E-BM cells compared to non-responders. At the same time 7/8 responders studied showed T cell mediated suppression of autologous CFU-c growth. T cell depletion experiments do not give predictive information on the outcome of IS therapy on admission. They may, however, be helpful to identify responders early post-treatment.

Adolescent↗
PubMed1985

Cyclosporin A (CyA) does not enhance CFU-c growth in patients with severe aplastic anaemia.

8 patients with severe aplastic anaemia (SAA) in remission following immunosuppressive therapy were studied for CFU-c growth from unfractionated or E-rosette depleted (E-) bone marrow (BM) cells. Cyclosporin A (CyA) was added to unfractionated BM cells at a concentration of 1000 ng/ml. The mean number of CFU-c/10(5) BM cells plated was 6 +/- 6 from unfractionated BM cells, 28 +/- 20 from E-BM cells, and 8 +/- 7 from unfractionated BM cells supplemented with CyA. All patients had significant increase of CFU-c growth after E rosette depletion (overall P = 0.002). On the contrary, only 1 patient showed an increase of CFU-c growth after addition of CyA, and overall there was no difference between untreated and CyA treated BM cells (P = 0.7). These results suggest that addition of CyA to BM cells in vitro is not an effective means of enhancing CFU-c growth in SAA patients.

Adolescent↗
PubMed1985

Bone marrow transplantation (BMT) for acute nonlymphoid leukemia (ANLL) in first remission.

20 patients with acute nonlymphoid leukemia (ANLL) in first remission were given cyclophosphamide, 120 mg/kg, followed by total body irradiation (TBI) and an HLA-identical allogeneic marrow transplant (BMT). TBI was delivered in a single dose (10 Gy on day -1) in 2 patients, or in fractionated doses (3.3 rad/day on days -3, -2, -1) in 18 patients. The median age of patients was 22 years (range 2-44). Median time from remission to BMT was 5 months (range 1-12). 5 patients died of transplant-related toxicity (graft-versus-host disease with or without interstitial pneumonia) and 15 are alive 7-77 months post-BMT (median 20). The actuarial 72 months survival is 73%. There has been one relapse in a 2-year-old child, 4 months post-BMT, in the marrow and in the testis. The 72-month actuarial disease-free survival is 68%. The actuarial probability of relapse is 7%. This study indicates that a high proportion of ANLL patients treated in first remission with fractionated TBI and allogeneic marrow transplantation can become long-term disease-free survivors.

Acute Disease↗
PubMed1985

T-derived colony-inhibiting activity: partial characterization and mechanism of action.

A soluble inhibitor of granulocyte macrophage colony growth, to which we shall refer to as T-derived colony-inhibiting activity (Td/CIA), was obtained from the supernatant of T cells from 5 healthy donors and 5 patients with severe aplastic anemia (SAA) in remission, following immunosuppressive therapy. The supernatants were purified by an ACA 44 column and the suppressor activity found in fractions of 70,000-80,000 daltons. Experiments were then performed to test for endogenous productions of Td/CIA in normal marrow cells (NBM), reversibility of suppression, and competitive inhibition with human placenta-conditioned medium (HPCM). The results of this study can be summarized as follows: the endogenous production of Td/CIA can be elicited by addition of mitogens to NBM, and is prevented if the marrow is T-depleted or treated with cyclosporin A; suppression is completely reversible if Td/CIA is removed from NBM by washing at 1, 48, 72 and 96 h; CFU-c which have been exposed to Td/CIA once, and freed from Td/CIA by washing, are still sensitive to a second exposure of Td/CIA; there is no clear competitive inhibition between Td/CIA and HPCM. These experiments represent an in vitro model of a lymphokine-mediated regulation of CFU-c growth not associated with death of progenitor cells.

Bone Marrow Cells↗
PubMed1985

Acute myelomonocytic leukemia. Demonstration of pulmonary involvement by bronchoalveolar lavage.

Massive pulmonary infiltration by leukemic cells resulting in respiratory symptoms is a rare complication of acute leukemia. We report the findings in a patient with acute myelomonocytic leukemia presenting with acute onset of fever, dyspnea, and nonproductive cough, in whom the diagnosis of pulmonary invasion by leukemic cells was made by cytochemical analysis of bronchoalveolar cells recovered by lavage.

Bronchi↗
PubMed1985

Effect of cyclosporin A (CyA) on the in vitro growth of hemopoietic progenitors from normal marrow.

Unfractionated normal bone marrow cells (NBM), adherent-cell-depleted NBM, and E-rosette-depleted NBM were plated in vitro for CFU-c or BFU-E formation at plateau concentrations of colony-stimulating activity (CSA) or erythropoietin, untreated or after preincubation with cyclosporin A (CyA). At concentrations of 1000 or 2000 ng/ml, CyA enhanced CFU-c growth up to 137 +/- 32% and 147 +/- 31% of expected baseline growth respectively (p = 0.005 and 0.001). When CyA was added to NBM depleted of T cells by rosetting once with sheep red blood cells (SRBC) there was no CFU-c enhancement at CyA concentrations of 1000 ng/ml, but enhancement could be seen at 2000-5000 ng/ml. The enhancing effect of CyA was completely abolished, however, when the SRBC rosetting procedure was repeated twice (95 +/- 37% of expected growth). On the other hand, removal of adherent cells was without effect on CFU-c enhancement mediated by CyA. The addition of CyA to NBM also enhanced the growth of BFU-E (256 +/- 182% of expected growth) (p = 0.001). The results of this study suggest that CyA can increase the plating efficiency of NBM cells, possibly by inhibiting an endogenous, T-cell-mediated, suppressor mechanism.

Bone Marrow Cells↗
PubMed1985

Cytochemical analysis of peripheral blood mononuclear cells following allogeneic bone marrow transplantation: correlation of hydrolase expression with graft-versus-host disease.

Peripheral blood mononuclear cells of 21 patients undergoing allogeneic bone marrow transplantation (BMT) were monitored post-BMT for immunologic markers (E rosettes OKT3, OKT8, DR, and BT5/9, a monoclonal antibody which stains helper T cells), cytochemical markers (acid phosphatase [AP], beta-glucuronidase [BGLU], and acid alpha naphthyl acetate esterase [ANAE] ), and morphology. The cytochemical T score, was obtained from typical AP, BGLU, and ANAE reactivity. The same was done for the cytochemical non-T score and macrophage (Mo) score. All patients received cyclosporine A (CyA) for graft-v-host disease (GvHD) prophylaxis. In univariate analysis there was no significant correlation between the proportion of E rosettes, OKT3-, OKT8-, DR-, and BT5/9-positive cells, and GvHD. The first three showed instead a positive correlation with time from transplant: E rosettes (P = .02), OKT3 (P = .01), and OKT8 (P = .003). In contrast, a significant negative correlation was found in univariate analysis, between the cytochemical T score and GvHD (P = .0001), and a positive correlation between non-T score and GvHD (P = .0008), as well as between the Mo score and GvHD (P = .03). There was no influence of time from transplant on the T (P = .8), non-T (P = .8), or Mo score (P = .4). In multivariate analysis comparing E rosettes, OKT3, T score, non-T score, GvHD, and time from BMT, the only variable associated with GvHD was the T score (P less than .05). These results suggest that T cell activation during GvHD is associated with a loss of hydrolase expression in T cells, but does not imply relevant modifications of immunologic surface markers. In addition, lysosomal enzymes appear early (before day 10) after transplantation, indicating that T cells at this stage are well differentiated.

Anemia, Aplastic↗
PubMed1985

Redistribution of arterial blood flow in metastases-bearing livers after infusion of degradable starch microspheres.

Changes in intrahepatic arterial blood flow after intraarterial injection of degradable starch microspheres (DSM) were studied in four patients undergoing hepatic arterial chemotherapy. All four livers contained metastases, three from colorectal cancer and one from melanoma. Using a CT scanner with a dynamic program, 8 mm liver sections were studied in each patient before and after the DSM infusion (180(-6) in 3 min). Density plots were obtained from 12 tumoral and 12 parenchymal areas after 5 ml push arterial injections of nonionic contrast medium. The areas under the curves (ID) were calculated. The ID after DSM infusion was reduced by 94% in a single hyperdense colorectal metastasis and by a mean of c. 82% in ten parenchymal areas. By contrast, nine hypodense colorectal metastases showed an average ID decrease of c. 156%. The ID of two melanoma metastases was reduced after DSM (-48% and -68%), while the ID of two matched parenchymal areas showed an approximately similar degree of increase (+36% and +64%). Since ID after contrast injection can be assumed to be a function of blood volume, mutual changes of parenchymal and tumoral blood flow appear to take place in metastases-bearing liver after arterial infusion of DSM. This phenomenon may be of diagnostic and therapeutic value for intraarterial chemotherapy of liver tumors.

Antineoplastic Agents↗
PubMed1984

Hairy cell leukemia: a retrospective study of 235 cases by the Italian Cooperative Group (ICGHCL) according to Jansen's clinical staging system.

This is a report from a cooperative study on hairy cell leukemia (HCL) involving 20 Hematology Departments in Italy. Data for the patients was collected between January 1967 and December 1981 and included 235 cases of which 203 could be evaluated; 160 were males (78.8%) and 43 females (21.2%) with an M:F ratio of about 3:1; mean age was 54 years (range 26-82 yrs). The diagnostic criteria of admission were: typical aspect of hairy cells, in peripheral blood and bone marrow smears, tartrate resistant acid phosphatase (TRAP) positivity, typical bone marrow, spleen, liver and/or lymph node histology, and/or electronmicroscopy. On the basis of hemoglobin level and spleen size at the time of diagnosis, three stages could be distinguished according to Jansen: 51 patients, 27 of which splenectomized, were in stage I; 67 patients, of which 44 splenectomized, were in stage II; 85 patients of which 60 splenectomized, were in stage III. The actuarial survival curves of these patients showed clear distinction between the three stages. In the first stage the difference in survival, between splenectomized and nonsplenectomized groups, was not statistically significant (p less than 0.5): on the contrary, in stages II and III the difference in survival was statistically significant (stages II and III; p less than 0.01).

Aged↗
PubMed1983

Effect of cannabis on enzyme induction by phenobarbital.

Cannabis extracts in olive oil administered s.c. to male adult rats decreases oxidizing microsomal enzymes measured as TPNH disappearance and AHH activity in liver postmitochondrial fraction (93.06% and 25.54% maximum inhibition respectively in chronic treatments). Simultaneous administration of single doses of cannabis extracts (330 mg/kg s.c.) and phenobarbital (100 mg/kg i.p.) causes impairment of total microsomal oxidases (86.83% inhibition) and decreases AHH (31.86% inhibition), thus blocking the enzyme induction by phenobarbital.

Animals↗
PubMed1983

Generation of CFU-c suppressor T cells. VI. Effect of cyclosporin A.

CFU-c suppressor T cells were generated in vitro by culturing overnight peripheral blood T cells from healthy donors with pokeweed mitogen (PWM), or T cells from patients with severe aplastic anemia (SAA) in remission, with culture medium (RPMI). The supernatants were removed the next morning, the cells harvested and washed, and both tested for CFU-c suppression on normal marrow cells. Cyclosporin A (CyA) was added to this system to test whether it could abrogate or prevent the generation of suppressor cells. CyA was incubated with T cells, at a concentration of 0.1 microgram/ml, for 30 min at 37 degrees C and then washed away, in two different assays: (a) before T cells were incubated overnight in culture medium with or without PWM, or (b) after T cells had been kept overnight in culture. The results of this study indicate that CyA can prevent the generation of CFU-c suppressor T cells if preincubated with both normal or SAA T cells prior to in vitro priming, whereas it cannot abrogate the suppressor activity of primed T cells.

Anemia, Aplastic↗
PubMed1983

NADPH-diaphorase used to estimate alterations in the toxic rapeseed oil syndrome.

The evaluation of NADPH-diaphorase in the post-mitochondrial fraction of rat liver has been shown a sensitive method to estimate alterations of microsomal oxidase systems in acute and chronic intoxications. It is also useful to demonstrate the interaction of drugs with barbiturates, which normally induce this enzyme. To study the biochemical liver damage which may occur in the toxic rapeseed oil syndrome, we measured NADPH-diaphorase in the post-mitochondrial fraction of rats given oral doses of toxic rapeseed oil (1 ml/day for 6 days), or oleil or linoleil anilide (10 mg/kg for 6 days). One-half the rats were sacrificed at the end of the dosing period and the other half were killed 4 weeks later. In both circumstances one-half the rats were treated with 2 doses of 80 mg phenobarbital/kg. NADPH-diaphorase was strongly inhibited by toxic oil and fatty acid anilides (72-93%). Phenobarbital induction was completely depressed. Enzyme activity remained depressed after a 4-week latency period.

Animals↗
PubMed1982

Generation of CFU-C suppressor T cells in vitro. V. A multistep process.

Different cell fractions obtained from five patients with immune severe aplastic anaemia (SAA) in complete autologous haematologic reconstitution were tested for CFT-c suppression. Bone marrow mononuclear cells (BMMC), but not peripheral blood mononuclear cells (PBMC), showed definite CFU-c inhibitory activity. On the contrary, both peripheral blood and marrow E rosetting cells (E+) suppressed CFU-c growth. The suppressor activity of PBE+ cells could not be rescued by adding back PBE- cells and/or PB adherent cells (AC). In addition, unfractionated PBMC exposed to sheep red blood cells (SRBC) suppressed CFU-c growth. PBMC from normal donors exposed to SRBC had no suppressor activity. This study suggests that CFU-c suppressor T cells in the peripheral blood of SAA patients are in different activation state as compared to BM cells from the same patients, and also differ from normal PB cells. The identification of T cells with different requirements for in vitro activation in order to exhibit a suppressor activity, suggests that generation of suppressor cells is a multistep process, and this may have practical implications for in vitro assays designed to test for immune suppression of haematopoiesis.

Anemia, Aplastic↗