Multilineage dysplasia without increased blasts identifies a poor prognosis subset of myelodysplastic syndromes.
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Blast Crisis↗
Biomedical subjects
A Pecci
Publications and source records attributed to A Pecci.
Expression of dipeptidylaminopeptidase IV/CD26 in peripheral blood lymphocytes of hemophilic subjects.
CD26 antigen, a 110 kDa membrane glycoprotein with exopeptidase activity (DAP IV), is an activation marker of T lymphocytes preferentially expressed on CD4+ memory cells and involved in T cell proliferation and IL-2 production after antigenic stimulation. We employed cytochemical and immunocytochemical techniques to study DAP IV/CD26 expression in circulating lymphocytes from 40 hemophilic patients, chronically treated with coagulation factors, in order to verify the possible involvement of this molecule in the immunological alterations of hemophilia. In all the hemophiliacs DAP IV activity was significantly lower than in the controls, independently of the quantity of blood transfused and previous exposure to viruses. This reduction may be responsible for the impaired proliferative response of lymphocytes to antigens and mitogens, notoriously observed in hemophilia. Whereas in the group of HIV- patients CD26 expression was similar to that of normal controls, in the 8 HIV+ hemophilic patients both percentages of positive lymphocytes and intensity of staining were significantly lower. In only 4 of the 8 cases was this deficit associated with CD4+ cell depletion. The significant selective loss of CD26 expression observed in HIV+ patients is probably an early event after HIV infection and seems to occur even before CD4 cell depletion. In conclusion, evaluation of DAP IV/CD26 might be a useful option for monitoring the immunological alterations of all hemophilic patients, HIV positive or not, chronically treated with coagulation factors.
Adolescent↗
International prognostic scoring system and other prognostic systems for myelodysplastic syndromes.
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Humans↗
Progestins prevent apoptosis in a rat endometrial cell line and increase the ratio of bcl-XL to bcl-XS.
Endometrial cell proliferation and cell death are regulated by ovarian hormones. The fall of ovarian progesterone in late secretory phase, or the artificial withdrawal of ovarian hormones during early pregnancy, are followed by programmed cell death of uterine epithelial cells. Aspects of this cell-specific response have been reproduced in a newly established rat endometrial cell line which expresses functional progesterone receptor. At low concentrations of serum and in the absence of glucocorticoids, these cells were dependent on progestins for survival. Removal of progesterone or addition of the antiprogestins RU38486 or ZK98299 led to a substantial increase of apoptotic cells indicated by the accumulation of internucleosomally degraded DNA. The hormonal control of cell proliferation and cell death correlated with the overall quantity and distribution of the different bcl-X transcripts. Progesterone administration not only increased total bcl-X mRNA level but also shifted the quantitative ratio between the different mRNA isoforms in favor for the apoptosis inhibiting form, bcl-XL, compared with the apoptosis promoting form, bcl-XS. These effects were rapid and could not be prevented by inhibitors of protein synthesis. As the low level of bcl-2 and bax mRNA was not influenced by progesterone treatment, the observed changes in total amount of bcl-X transcripts and spliced isoforms could represent the mechanism by which progesterone controls cell death in epithelial cells of the endometrium.
Animals↗
Endothelin-1-induced incorporation of cholesterol into rat adrenals.
The effect of endothelin-1 (ET-1) on cholesterol uptake by adrenal cortex was evaluated through several experimental approaches: infusion of ET-1 followed by measurement of endogenous cholesterol in excised adrenals; infusion of ET-1 followed by tritiated cholesterol incorporation into adrenal quarters in vitro; coinfusion of ET-1 with tritiated cholesterol-enriched serum and determination of adrenal-associated radioactivity; and tritiated cholesterol incorporation in incubations of adrenal cells. In all cases ET-1 increased cholesterol uptake. Subcellular fractionation showed an ET-1-mediated augmentation in mitochondrial fraction. This increase was mediated by the subpopulation B of adrenal receptors for ET-1. In addition, ET-1 also increased cytochrome P450-SCC (side-chain cleavage) activity.
Adrenal Glands↗
Effects of staurosporine on ACTH-mediated stimulation of aldosterone production.
Incubation of rat adrenal glomerulosa cells with low concentrations (up to 50 nM) of the protein kinase (PKC) inhibitor staurosporine (ST) inhibited aldosterone (ALDO) and cyclic AMP (cAMP) production stimulated by adrenocorticotropic hormone (ACTH) and cholera toxin. Only higher concentrations (1.6 microM) of staurosporine inhibited dibutyryl-cAMP- and forskolin-induced stimulation of aldosterone production. cAMP levels were increased only with low concentrations of the PKC inhibitor. This latter increase was avoided by treatment with a maximal concentration of isobutylmethylxanthine (MIX). Our results suggest that: (1) second messengers other than cAMP are involved in ACTH action; (2) staurosporine inhibits different kinases involved in ACTH action in a dose-dependent manner; (3) the protein kinase inhibited by high concentrations of staurosporine appears to be the cAMP-dependent kinase, PKA; and (4) the protein kinase inhibited by low concentrations of staurosporine remains to be identified. This latter species is suggested as being involved in mediating ACTH-induced activation of Gs.
Adrenocorticotropic Hormone↗
Endothelin-1 stimulation of aldosterone and zona glomerulosa ouabain-sensitive sodium/potassium-ATPase.
Endothelin stimulates the cells of the zona glomerulosa of the adrenal gland and releases aldosterone. While it is a less potent aldosterone secretagogue than angiotensin II endothelin also potentiates the effects of angiotensin II on aldosterone biosynthesis. Two endothelin receptors have been cloned and are expressed in the adrenal zona glomerulosa. Intravenous infusion of endothelin at a rate of 80 ng/kg/min for 30 min into rats produced increases in blood pressure, adrenal content of aldosterone and stimulated the ouabain-sensitive sodium potassium ATPase in the zona glomerulosa, but not in the zona fasciculata, of the adrenal. The simultaneous infusion of the isopeptide specific endothelin receptor A (ETA) antagonist BQ-123 blocked the pressor effects of endothelin, but did not alter the increase in aldosterone content of the zona glomerulosa or the ouabain-sensitive sodium potassium ATPase activity. Infusion of Sarafotoxin 6b, an ETB agonist, also increased the aldosterone content of the adrenal and stimulated the ouabain-sensitive sodium potassium ATPase in the zona glomerulosa, further indicating that the effect of endothelin is probably mediated by ETB or isopeptide non-specific endothelin receptor. The mechanism by which endothelin stimulates the sodium potassium ATPase is unclear as is the relation between a stimulated sodium potassium ATPase and the potentiation of angiotensin II effect on the adrenal.
Aldosterone↗
In vivo stimulation of aldosterone biosynthesis by endothelin: loci of action and effects of doses and infusion rate.
Infusion of endothelin-1 (ET-1) into rats increased adrenal mitochondrial synthesis of aldosterone from deoxycorticosterone and the adrenal cytosolic content of aldosterone. The dose-response relationships for these last two effects of ET-1 were found to be biphasic with a maximum (corresponding to 80 to 200% increase) at 50 to 80 ng ET-1/kg/min, and were also dependent on the infusion rate. Plasma aldosterone levels were also increased in a similar ratio. Previous infusion of the converting enzyme inhibitor enalapril did not affect the ET-1-induced increase in steroidogenesis. Finally, pregnenolene production was also increased in incubations of mitochondria from treated rats. These results indicate that ET-1 augments aldosteronogenesis by increasing the early as well as the late pathway. These effects were independent of the formation of angiotensin II. Isolated glomerulosa cells responded to ET-1 increasing aldosterone production in a dose-related fashion. These results confirm a direct effect of ET-1 on the adrenal gland in vivo.
Aldosterone↗
Immunologic profile in patients with Hodgkin's disease in complete remission.
Mononuclear cell subsets in peripheral blood, in vitro production of interleukin-2 (IL-2) and gamma interferon (IFN gamma), spontaneous cell-mediated cytotoxicity (SCMC) and circulating levels of Type I IFN, neopterin, beta-2 microglobulin (B2-M), immunoglobulins and complement fractions were studied in 33 patients with Hodgkin's disease (HD) in complete remission. The mean percentages, but not the absolute numbers, of T-lymphocytes expressing pan-T markers (OKT11, OKT3, ER, E-AET R) were significantly decreased compared with control values. Furthermore, patients showed a selective loss of OKT4+ cells, as well as increased percentages and numbers of Leu7+ and OKIa+ lymphocytes, and of OKM1+, LeuM2+, and LeuM3+ cells. OKT4+ cell depletion was a characteristic of patients with shorter time since beginning of remission as well as of those with nodular sclerosis (NS), mixed cellularity Hodgkin's disease (MC-HD), and systemic symptoms at diagnosis. Multifactorial statistical analysis carried out to investigate the effect of disease characteristics and the time since remission began on peripheral mononuclear blood cell (PMBC) subsets showed that histologic condition was the single best predictor of T-cell pool or OKT4+ cell subset size. Time since remission duration and other disease-related factors determined differences in the percentages, but not in the absolute numbers, of T-cell fractions. In addition, neither the disease features nor the time since remission duration determined significant differences in the absolute number of non-T-mononuclear cells in the various patient groups. Patients displayed decreased in vitro synthesis of IL-2 and IFN gamma. The values of SCMC, Type I IFN, neopterin, B2-M, immunoglobulins, and complement fractions did not differ greatly from those of controls.
Adult↗
Preliminary observation on the clinical tolerance of interferon-beta in cancer patients.
Nine patients with metastatic solid tumors were given IFN-beta by i.v. bolus injections. Six escalating doses (from 1 to 9 X 10(6) IU) followed by 6 additional injections at the dose of 9 X 10(6) IU were administered every other day (schedule A) in 3 of the 9 patients. IFN dose was also increased to a maximum of 46 X 10(6) IU, and 12 individual injections of 1, 2, 3.3, 5, 7, 9, 12, 16, 21, 27, 34 and 46 X 10(6) IU of IFN were given over a minimum of a 24-day period (schedule B) in 6 of the 9 patients. The single maximal tolerated dose ranged from 9 to 46 X 10(6) IU. The toxicity of IFN-beta given as scheduled in this study was significant but acceptable.
Adult↗
Discrimination of various contributions to the absorbed dose in BNCT: Fricke-gel imaging and intercomparison with other experimental results.
A method is described for the 3D measurements of absorbed dose in a ferrous sulphate gel phantom, exposed in the thermal column of a nuclear reactor. The method, studied for Boron Neutron Capture Therapy (BNCT) purposes, allows absorbed dose imaging and profiling, with the separation of different contributions coming from different secondary radiations, generated from thermal neutrons. In fact, the biological effectiveness of the different radiations is different. Tests with conventional dosimeters were performed too.
Boron Neutron Capture Therapy↗
Rare immunological presentation in B-cell chronic lymphocytic leukaemia.
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Adult↗
Bone marrow necrosis in acute lymphoblastic leukemia.
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Aged↗
Idarubicin and cytosine arabinoside in the induction and maintenance therapy of high-risk myelodysplastic syndromes.
BACKGROUND AND OBJECTIVE: Recently, the results of a few pilot studies have shown the efficacy of the association of idarubicin (IDA) and cytosine arabinoside (Ara-C), already successfully employed in acute myeloid leukemia (AML), for remission induction in patients with myelodysplastic syndrome (MDS). We set out to evaluate in a multicenter study the efficacy and tolerability of an intensive therapy with IDA and Ara-C in patients with RAEB and RAEB-t, the rate and duration of CR and the overall survival in adults treated with full doses and in the elderly treated with lower doses; furthermore, we investigated the efficacy of low-dose maintenance chemotherapy. METHODS: Pretreated adult patients with de novo RAEB and RAEB-t, meeting at least one of the following criteria, were included: neutrophils < 0.5 x 10(9)/L or moderate neutropenia with infectious episodes, platelets < 30 x 10(9)/L or moderate thrombocytopenia but with bleeding symptoms, transfusion > 4 red cell units/months, rapid increase of bone marrow blasts. Induction treatment consisted of a cycle with IDA and Ara-C. Adult patients less than 65 years old were treated with the following doses: Ara-C 1 g/m2/day i.v. 6-hour infusion, on days 1-4, IDA 10 mg/m2/day i.v., on days 1-3. Elderly patients (> or = 65 yrs) were treated with lower doses: Ara-C 1 g/m2/day 6 hours infusion, on days 1 and 2, IDA 10 mg/m2/day i.v., on days 1 and 2. Responders followed a consolidation course identical to induction. RESULTS: From February 1994 to February 1997, 25 patients were enrolled, 20 males and 5 females aged between 22 and 76, 10 were > or = 65 years old, 7 had RAEB and 18 had RAEB-t. Twelve cases (48%) achieved complete remission (CR), 7 cases (28%) achieved partial remission, 4 patients were resistant and two patients (8%) died during the aplastic phase. A significantly higher CR rate was found in younger patients (p = 0.036), while gender, FAB subtype, presence of Auer rods, cytogenetic findings, and the interval from diagnosis to treatment did not significantly influence CR achievement. INTERPRETATION AND CONCLUSIONS: Our results show that in de novo RAEB and RAEB-t, the employed treatment with IDA and Ara-C is associated with satisfactory frequency of response with acceptable toxicity.
Adult↗
Idarubicin and cytosine arabinoside in the induction and maintenance therapy of high-risk myelodysplastic syndromes.
BACKGROUND AND OBJECTIVE: Recently, the results of some pilot studies have shown the efficacy of the association of idarubicin (IDA) and cytosine arabinoside (Ara-C), already successfully employed in acute myeloid leukemia (AML), for remission induction in patients with myelodysplastic syndrome (MDS). We set out to evaluate in a multicenter study the efficacy and tolerability of an intensive therapy with IDA and Ara-C in patients with RAEB and RAEB-t, the rate and duration of complete remission, and the overall survival in adults treated with full doses and in the elderly treated with lower doses; furthermore, we investigated the efficacy of low-dose maintenance chemotherapy. METHODS: Pretreated adult patients with de novo RAEB and RAEB-t, meeting at least one of the following criteria, were included: neutrophils < 0.5 x 10(9)/L or moderate neutropenia with infectious episodes, platelets < 30 x 10(9)/L or moderate thrombocytopenia with bleeding symptoms, transfusion > 4 red cell units/months, rapid increase of bone marrow blasts. Induction treatment consisted of a cycle with IDA and Ara-C. Adult patients less than 65 years old were treated with the following doses: Ara-C 1 g/m2/day i.v. 6-hour infusion, on days 1-4, IDA 10 mg/m2/day i.v., on days 1-3. Elderly patients (> or = 65 yrs) were treated with lower doses: Ara-C 1 g/m2/day 6 hours infusion, on days 1 and 2, IDA 10 mg/m2/day i.v., on days 1 and 2. Responders followed a consolidation course identical to induction. RESULTS: From February 1994 to February 1997, 25 patients were enrolled, 20 males and 5 females aged between 22 and 76, 10 were > or = 65 years old, 7 had RAEB and 18 had RAEB-t. Twelve cases (48%) achieved complete remission (CR), 7 cases (28%) achieved partial remission, 4 patients were resistant and two patients (8%) died during the aplastic phase. A significantly higher CR rate was found in younger patients (p = 0.036), while gender, FAB subtype, presence of Auer rods, cytogenetic findings, and the interval from diagnosis to treatment did not significantly influence CR achievement. INTERPRETATION AND CONCLUSIONS: Our results show that in de novo RAEB and RAEB-t, treatment with IDA and Ara-C is associated with satisfactory frequency of response with acceptable toxicity.
Adult↗