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Biomedical subjects

A Pinto

Publications and source records attributed to A Pinto.

At least 253 records · Page 14Linked to original sources
PubMed1993

[Prevalence of hepatitis C virus antibodies in chronic hemodialysis and kidney transplantation patients].

Hepatitis C virus antibodies were measured in 26 chronic hemodialyzed patients and 43 kidney transplant recipients, using a second generation ELISA method. Fifty four percent of hemodialyzed had a longer duration of dialysis treatment compared with patients with negative antibodies (57.6 +/- 30.5 vs 15.4 +/- 7.3 months), and did not differ in the number of transfusions. Seven patients had elevated serum transaminase values, all with positive antibodies. Thirty five percent of kidney transplant recipients had positive antibodies. In these subjects, no relation was observed between the number of transfusions or length of dialysis treatment and the presence of positive hepatitis C antibodies.

Adult↗
PubMed1993

5-Aza-2'-deoxycytidine (Decitabine) induces trilineage response in unfavourable myelodysplastic syndromes.

The preliminary results of a disease-oriented phase I-II study aimed at evaluating the clinical activity of 5-aza-2'-deoxycytidine (Decitabine) in patients affected by advanced myelodysplastic syndromes (MDS) are reported. Two patients affected by refractory anemia with excess of blasts (RAEB) and eight with RAEB in transformation (RAEB-T) were treated with Decitabine at a daily dose of 45 mg/m2, divided into three 4 h infusions for 3 days (six patients) or as continuous infusion of 50 mg/m2 for 3 days (four patients). Treatment with Decitabine resulted in a significant increase in circulating neutrophils, platelets, and hemoglobin with respect to pretreatment values in over 50% of patients. These changes were accompanied by the improvement of the marrow myeloid relative differentiation index (median fivefold increase in the whole group of patients) and of the myeloid to erythroid cell ratio (median twofold increase) in most of the patients. In four out of ten patients a complete normalization of peripheral blood (PB) and bone marrow (BM) picture (complete hematologic response) was obtained. The evaluation of the percentage of CD34-positive BM cells showed a slow but progressive reduction of early leukemic progenitors in most of the patients. A transient slight BM hypoplasia was obtained in less than 50% of patients while a severe marrow aplasia was never observed in our group of MDS patients during treatment with Decitabine. Extra-hematological toxicity was very mild in all the patients. The preliminary results of our study indicate that Decitabine is able to induce trilineage hematological responses in advanced MDS patients along with a stable normalization of the PB and BM picture in some of the subjects. Decitabine appears an active agent in advanced MDS and this deserves careful investigation in this heterogeneous group of disorders.

Aged↗
PubMed1993

Pilot study of 5-aza-2'-deoxycytidine (Decitabine) in the treatment of poor prognosis acute myelogenous leukemia patients: preliminary results.

5-Aza-2'-deoxycytidine (Decitabine) is a new cytosine analog with potent antileukemic activity and able to induce in vitro gene activation and cellular differentiation by a mechanism probably involving DNA hypomethylation. The aim of this pilot study was to evaluate the efficacy and the toxicity of Decitabine, used as single induction agent, in the treatment of poor prognosis acute myeloid leukemia (AML) patients, and to explore its mechanism of action. A total of 12 patients were treated with Decitabine at 90-120 mg/m2 as a four hour intravenous infusion, three times daily for three consecutive days every four to six weeks. A minimum of two courses were required for response evaluation and to consider a patient as therapeutic failure. A total of 10/12 patients were fully evaluable for response; three patients achieved a complete remission (CR) and one a partial remission (PR). Extra-hematological toxicity was generally mild. As for the mechanism of action, both a differentiation induction effect and a cytotoxic mechanism have been observed. In particular, CRs and PRs were probably obtained through the induction of leukemia cell differentiation as shown by the kinetic of remission and immunotyping studies. The preliminary results of this ongoing study suggest that Decitabine may have a prominent role in the treatment of those AML patients with poor general conditions and/or advanced age.

Aged↗
PubMed1993

In vitro and in vivo effects of 5-aza-2'-deoxycytidine (Decitabine) on clonogenic cells from acute myeloid leukemia patients.

5-Aza-2'-deoxycytidine (Decitabine) is an analog of deoxycytidine now entering clinical trials in acute myeloid leukemia (AML) owing to a defined antileukemic activity mediated at least in part by DNA hypomethylation, altered gene expression, and induction of cell differentiation. In the present study, we examined the relationship between the in vitro sensitivity to Decitabine of blast progenitors and the clinical outcome, in nine AML patients treated in vivo with Decitabine within a phase II trial carried out at two different institutions. Leukemic blast progenitors in acute myeloid leukemia (AML) undergo terminal divisions giving rise to colonies in methylcellulose. The self-renewal capacity of blast progenitors is conversely reflected by a secondary methylcellulose assay after exponential growth of clonogenic cells in suspension cultures. Three out of four patients, in which clonogenic cells in methylcellulose were strongly suppressed by Decitabine and clonogenic growth of blasts cultured in suspension was only slightly affected, failed on Decitabine treatment in vivo. Two subjects, whose blast progenitors in suspension culture were significantly inhibited by Decitabine, obtained a positive hematological response (complete or partial remission, CR or PR) and an additional patient showing a similar in vitro pattern died in induction with an hypoplastic marrow without morphological evidence of persistant leukemia. Interestingly two patients displaying an unfavourable in vitro pattern (i.e. a minor suppression of self-renewal mitoses as evinced from suspension cultures) achieved a hematological response (CR and PR) upon in vivo therapy with Decitabine. The in vitro response to Decitabine of clonogenic progenitors from both these patients shifted to a favourable pattern (i.e. major suppression of self-renewal versus terminal mitoses) following manipulation of culture conditions by the addition or removal of exogenous growth factors. In addition, in a further patient refractory to treatment with Decitabine in vivo, similar alterations of the culture conditions were unable to modify the unfavourable pattern of response to the drug in vitro. Our results indicate that the sensitivity of blast progenitors in suspension cultures strongly correlates with the remission outcome of the patients. From our data, it also appears that alterations of culture microenvironment are able to modify the response of AML blasts to Decitabine, unveiling the 'hidden' sensitivity of leukemic progenitors to the drug in cases characterized by a discrepancy between in vivo and in vitro results, i.e. apparent in vitro resistance and favourable clinical outcome.

Acute Disease↗
PubMed1993

Cognitive correlates of depressive symptoms in hospitalized adolescents.

This study examined the relationship between self-reported depression and cognitive style in adolescent inpatients. Attributional style, perceived control over environmental events, and hopelessness were assessed in 80 consecutive admissions to an adolescent psychiatric unit. BDI scores were used to classify 36 patients as depressed and 44 as nondepressed. Adolescents who reported depression also reported significantly more internal attributions for negative events and less internal attributions for positive events, evidenced a more external locus of control, and described themselves as significantly more hopeless than did the nondepressed adolescents. Hopelessness and internal attributions for negative events were the strongest predictors of depressive symptoms. In contrast to the findings of most studies using clinical populations of depressed children and adolescents, a maladaptive cognitive style and self-reported depression were highly, positively correlated.

Adolescent↗
PubMed1993

Effect of some products of protein catabolism on the endothelium-dependent and -independent relaxation of rabbit thoracic aorta rings.

We have investigated the effect that some products of protein catabolism have on endothelium-dependent and -independent relaxation of rabbit aorta rings precontracted with phenylephrine (PE). All the products tested, i.e., creatinine (CRT), guanidinosuccinic acid (GSA), urea (UR), guanidine (GND) and methylguanidine (MG), are structurally related to L-arginine (L-ARG), the substrate for nitric oxide (NO) biosynthesis which accounts for the biological properties of endothelium-derived relaxing factor (EDRF). Endothelium-derived NO (EDNO) release was induced by agents acting via a receptor- [acetylcholine (ACh)] or a nonreceptor-mediated mechanism (calcium ionophore A23187), and the endothelial-independent relaxation was induced by the NO donor glyceryl trinitrate (GTN). CRT (0.1-10 mM) did not modify the endothelium-dependent relaxation caused by ACh or A23187 but produced a small increase in the response to the endothelium-independent vasorelaxant GTN. Concentrations of GSA up to 1 mM did not affect the relaxation of rabbit aortic rings induced by either ACh or A23187, but at 10 mM, GSA enhanced the relaxation produced by these agents. UR (1-100 mM) inhibited, in a concentration-dependent manner, the relaxation induced by ACh, but not that caused by A23187 or GTN. By comparison, GND and MG (0.1-10 mM) produced a concentration-related inhibition of both ACh- and A23187-induced relaxation. The inhibition by these compounds was either completely or partially reversed by L-ARG. In contrast, the relaxation induced by GTN was inhibited only by higher concentrations (10 mM) of GND or MG. These results indicate that some products of protein catabolism can reduce EDNO formation in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A new variant of lethal neonatal short-limbed platyspondylic dwarfism.

This article describes an unusual skeletal dysplasia in a male fetus diagnosed by ultrasound at 18 weeks of gestation. The clinical and radiologic findings resemble thanatophoric dysplasia. Histologic examination revealed abnormalities in the resting cartilage, physeal growth plate, and bone. The resting cartilage contained peculiar large chondrocytes with huge lacunae. The growth plate revealed absence of column formation and hypertrophic vacuolated chondrocytes extending far into the metaphyseal bone trabeculae. The bone was hypercellular with absence of lamellar bone. The cortical bone was scanty and woven. The histopathologic features are, therefore, unique and differ from all other well-recognized varieties of short-limbed platyspondylic dwarfism.

Bone and Bones↗
PubMed1992

Inhibition of the self-renewal capacity of blast progenitors from acute myeloblastic leukemia patients by site-selective 8-chloroadenosine 3',5'-cyclic monophosphate.

The physiologic balance between the two regulatory subunit isoforms, RI and RII, of cAMP-dependent protein kinase is disrupted in cancer cells; growth arrest and differentiation of malignant cells can be achieved when the normal ratio of these intracellular signal transducers of cAMP is restored by the use of site-selective cAMP analogs. In this study we evaluated the effects of the site-selective cAMP analog 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cAMP) on clonogenic growth of blast progenitors from 15 patients with acute myeloblastic leukemia and 3 patients affected by advanced myelodysplastic syndrome. Leukemic blast progenitors undergo terminal divisions, giving rise to colonies in methylcellulose. The self-renewal capacity of blast progenitors is conversely reflected in a secondary methylcellulose assay after exponential growth of clonogenic cells in suspension cultures. In all the samples tested, 8-Cl-cAMP, at micromolar concentrations (0.1-50 microM), suppressed in a dose-dependent manner both primary colony formation in methylcellulose and the recovery of clonogenic cells from suspension culture. Strikingly, in the samples from the entire group of patients, 8-Cl-cAMP was more effective in inhibiting the self-renewing clonogenic cells than the terminally dividing blast cells (P = 0.005). In addition, in four out of six cases studied, 8-Cl-cAMP was able to induce a morphologic and/or immunophenotypic maturation of leukemic blasts. An evident reduction of RI levels in fresh leukemic cells after exposure to 8-Cl-cAMP was also detected. Our results showing that 8-Cl-cAMP is a powerful inhibitor of clonogenic growth of leukemic blast progenitors by primarily suppressing their self-renewal capacity indicate that this site-selective cAMP analog represents a promising biological agent for acute myeloblastic leukemia therapy in humans.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

B-zone small lymphocytic lymphoma: a morphologic, immunophenotypic, and clinical study with comparison to "well-differentiated" lymphocytic disorders.

The pathologic, immunologic, and clinical features of five cases of B-zone small lymphocytic lymphoma (BZSLL), characterized by a nondestructive growth pattern with a selective and complete replacement of the B-zone areas of lymph nodes, were examined. These findings were compared with those of 13 cases of intermediate differentiated lymphoma/mantle zone lymphoma (ILL/MZL) and 20 cases of typical small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). B-zone SLL was characterized histologically by a deceptively benign pattern at a low magnification, the lymph node architecture being substantially preserved, in contrast to the ILL/MZL and SLL/CLL cases, in which complete effacement of the normal architecture usually could be observed. Moreover, in BZSLL the cellular population was rather uniform and lacked either a prolymphocytic component or the small-cleaved lymphoid cells often seen in SLL/CLL and ILL/MZL cases, respectively. The phenotypic profile of the BZSLL clonal cell population studied by the immunoperoxidase method and by single- and double-labeling flow cytometric analyses (SIg+, CD19+, CD20+, CD21+, CD22+, CD24+, CD35+, CD37+, CD74+, CD45+, CD45R+, MB2+, HLA-DR+, Leu-8+, CD9+/-, CDw75+/-, CD5-/+, CD23-/+, CD10-, FMC7-, PCA-1-, CD25-, CD38-, CD43-, CD3-) appeared to be fairly homogeneous and sufficiently distinct from that of ILL/MZL, based on the absence of FMC7 and CD38 molecules, and from that of SLL/CLL due to significantly stronger expression of SIgs (P less than .05), the higher reactivity with anti-CD9 and -CD22 antibodies (P less than .05), the lower reactivity with anti-CD5 and -CD23 antibodies (P less than .05), and the absence of CD25 determinants. Several clinical features of patients with BZSLL, including age group, advanced stage disease, and high frequency of bone marrow and peripheral blood involvement, were similar to those found in the other patients with ILL/MZL and SLL/CLL, but none of the BZSLL patients had an absolute lymphocyte count higher than 15.0 x 10(9)/L at presentation. Based on the architectural pattern, cytologic features, immunophenotypes, and hematologic findings, we conclude that BZSLL is an unusual variant of SLL that is primary in the lymph nodes and should be distinguished from ILL/MZL and CLL.

Adult↗
PubMed1992

Phorbol ester induced osteoclast-like differentiation of a novel human leukemic cell line (FLG 29.1).

Studies on human osteoclast formation have been hampered by lack of a defined isolated progenitor cell population. We describe here the establishment of a human leukemic cell line (designated FLG 29.1) from bone marrow of a patient with acute monoblastic leukemia. The cultured cells are predominantly undifferentiated leukemic blasts, but addition of 12-o-tetradecanoylphorbol 13-acetate (TPA; 0.1 microM) induces irreversible differentiation into adherent, non-dividing, multinucleated cells. TPA-treated cells bear surface antigens typical of fetal osteoclasts, degrade 45Ca-labeled devitalized bone particles, display tartrate-resistant acid phosphatase in both mononuclear and multinuclear cells and receptors for calcitonin. Calcitonin increases intracellular cAMP accumulation in TPA-treated cells. TPA-treated cells show some ultrastructural features of osteoclasts as evidenced by transmission EM. These results indicate that FLG 29.1 cells may represent an osteoclast committed cell population, which upon induction with TPA acquire some morphological, phenotypical, and functional features of differentiated osteoclasts.

Antigens, CD↗
PubMed1992

Follicular lymphoma of compartmentalized small cleaved center cells and mantle zone lymphocytes. Evidence for a common derivation.

The authors have observed a unique case of follicular lymphoma in which the central zones of neoplastic nodules were composed predominantly of small cleaved cells (SCC) that were surrounded by small lymphoid cells proliferating in wide mantles as in mantle zone (MZ) lymphoma. The central SCC component displayed a follicular SCC lymphoma-like phenotype (IgD-, CD10+, CD5-, CD68-), whereas the neoplastic cells of the peripheral zones had an MZ lymphoma-like phenotypic profile (IgD+, CD10-, CD5+, CD68+). In extranodal involved tissues, either follicular or diffuse (leukemic-like) patterns of lymphoma infiltration were noted. Flow cytometric analyses showed in the bone marrow or the peripheral blood two leukemic B cell populations, one mimicking the phenotypic profile (IgM+, IgD+, CD5+, CD10-, Leu8-) of small lymphoid cells with MZ-like features, and the other with phenotypic features (IgM+, IgD-, CD5+, CD10+, Leu8+) intermediate between those of MZ-like cells and those of the SCC component (follicular center-like) detected in the lymph node. Immunomagnetic sorting and gene rearrangement studies indicated that both CD10+ and CD10- B lymphocytes and lymph node neoplastic B cells shared the same clonal origin. This unusual follicular lymphoma can be viewed as the result of the proliferation of a single follicular progenitor capable of differentiating toward both a germinal center and an MZ phenotype. The simultaneous presence in the same patient of at least three neoplastic B-cell populations at different maturation stages, encompassing follicular center and MZ phenotypes, and showing the same clonal derivation, indicates a close lineage relationship between follicular SCC and MZ lymphomas.

Aged↗
PubMed1992

Regression of structural vascular changes in hypertensives after captopril treatment.

In order to investigate whether hypertension-related structural vascular changes may be influenced by antihypertensive treatment, 10 patients were studied suffering from essential arterial hypertension, five males and five females, aged between 34 and 61 years (mean age: 46.9 +/- 8.13 years). All patients received a placebo for 1 week and then captopril, 75 mg b.i.d. for 3 months. After placebo and captopril treatments, the following parameters were evaluated: SBP, DBP, mean blood pressure (MBP), by the formula 1/3 (SBP + 2 x DBP) and basal and minimal vascular resistances, respectively obtained by the ratios MBP/rest flow and MBP/peak flow. Blood flows have been obtained by strain gauge plethysmography. A significant decrease in systolic (P less than 0.025), diastolic (P less than 0.01) and mean blood pressure (P less than 0.01), basal vascular resistances (52 +/- 19 vs 28 +/- 12 A.U., P less than 0.01) and minimal vascular resistances (6.3 +/- 2.2 vs 3.9 +/- 2.8 A.U., P less than 0.025) has been observed after captopril treatment in comparison to placebo, whereas rest (2.9 +/- 0.7 vs 4.1 +/- 0.9 ml.min-1.100 g-1, P less than 0.01) and peak blood flows (21.3 +/- 5.8 vs 29.7 +/- 9.4 ml.min-1.100 g-1) significantly increased. These data seem to indicate that antihypertensive treatment with the angiotensin-converting enzyme inhibitor, captopril, is not only efficacious in inducing a significant blood pressure decrease, consequent to the reduction of basal vascular resistance (due to the vasodilating effects of the drug), but is also able to reduce minimal vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Time course of PAF formation by gastrointestinal tissue in rats after castor oil challenge.

When castor oil was administered by gavage to rats, the duodenum and jejunum, but not the stomach, produced large amounts of platelet activating factor 3-7 h after oil challenge with a peak at 3 h. Intraluminal release of acid phosphatase was also markedly increased in the duodenum and jejunum of castor oil-treated rats, especially 3-5 h after oil challenge. No increase was observed in the stomach. There was a correlation between elevated release of acid phosphatase and intestinal hyperaemia.

Acid Phosphatase↗