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Biomedical subjects

A Pinto

Publications and source records attributed to A Pinto.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Three quantitative studies of gender and identity in psychotherapy consultations.

This paper details the application of three distinctive approaches to the analysis of line-by-line scores for themes of gender and identity in recorded psychotherapy consultations conducted by three male analysts with a female patient. The first method involved commonly used statistical comparisons of the frequency with which gender subthemes and allusions to identity appeared in each consultation session. The results of this study indicate three significantly different patterns of gender material in the communications from the patient with each of the analysts who interviewed her--and from each analyst and patient/analyst system as well. Therapist dominance in this area appeared to be quite strong. The second study involved measures of overall informational complexity for various aspects of the gender/identity sequence of communications. Here too, individual differences emerged. They not only add to the evidence for therapist dominance in these protocols, but also provide indications that sessions differ in respect to the extent to which the information they contain is ordered and repetitive or redundant, as compared to disordered, complex, and varied. The third study availed itself of stochastic methods in which the Box-Jenkins models were used to define mathematically and post hoc, the deeper structure of aspects of the vicissitudes of gender/identity expressions in the course of these consultations. The main finding was that change in speaker role in respect to these themes accelerated in response to random interventional shocks to the system that occurred at the time of measurement and inversely with shocks to the system sustained the previous second. This look into the deeper structure of these sequences revealed considerable sensitivity to recent shocks to the patient/therapist system, much underlying instability, and strong tendencies toward establishing stability or equilibrium when the system destabilized. Of note is the finding that all three consultations, by and large, followed the same configuration--itself a rarely seen model. The implications and promise of these methods are discussed.

Adult↗
PubMed1992

[Effects of therapy with bis-hemisuccinate of ursodeoxycholic acid bisodium salt in patients with chronic hepatitis].

It has recently been shown that ursodeoxycholic acid administration improves liver function tests in patients with chronic liver diseases. Aim of the present study was to evaluate an ursodeoxycholic acid derivative (bis-hemisuccinate bisodic salt Ursodamor, Farmaceutici Damor, Napoli) in patients with chronic hepatitis. Forty patients (15 M, 25 F) with biopsy proven chronic liver disease participated to the study. Patients were randomly allocated to two treatment groups. Twenty patients (4 PBC, 11 CAH/CPH, 5 cirrhosis) received the ursodeoxycholic acid derivate at the dose of 600 mg/day, while 20 patients (1 PBC, 11 CAH/CPH, 8 cirrhosis) received a placebo. For both groups the treatment period was six months. ALT serum levels were significantly reduced in the treated group (from 84 +/- 14 to 62 +/- 14 p less than 0.0005) while no significant change was observed in the placebo group. In the treated group but not in the placebo group alkaline phosphatases and gamma-GT were also significantly reduced (from 268 +/- 56 to 160 +/- 23 p less than 0.0005 and from 79 +/- 21 to 45 +/- 10 p less than 0.0005). In conclusion, our results suggest that the administration of the ursodeoxycholic acid derivate, bis-hemisuccinate, bisodic salt, improves liver function tests in patients with chronic liver hepatitis. Similarly to ursodeoxycholic acid this new derivate probably interferes with bile acid pool composition by replacing the more detergent and probably more toxic endogenous bile acid.

Alkaline Phosphatase↗
PubMed1992

Giant cell fibroblastoma in childhood immunohistochemical and ultrastructural study.

Two cases of giant cell fibroblastoma in children are presented. Histologic features included a dense fibrous tissue stroma with multinucleated giant cells lining sinusoid-like spaces. Immunohistochemical stains and electron microscopy provide evidence of a fibroblastic origin of the tumor cells. Ultrastructure of the multinucleated cells revealed segmentation of the nuclei with multiple centrioles, suggesting that an abnormality in the division of the tumor cells may be the mechanism for the formation of the giant cells.

Breast Neoplasms, Male↗
PubMed1992

Fatal neonatal pneumonia caused by adenovirus type 35. Report of one case and review of the literature.

A 3680-g term male neonate developed bilateral bronchopneumonia at 9 days of age. The labor, delivery, and immediate postnatal period had been unremarkable. Despite standard antibiotic therapy, the patient progressed to respiratory failure and died 4 days later. Adenovirus particles were found in oropharyngeal secretions 1 day prior to death. Autopsy revealed an extensive necrotizing bronchiolitis and alveolitis with frequent "smudge cells." Adenovirus was identified by culture, electron microscopy, and in situ DNA hybridization. The adenovirus was serotyped as type 35, which, to our knowledge, has not been previously described in neonatal adenovirus pneumonia.

Adenovirus Infections, Human↗
PubMed1991

Expression of myelomonocytic antigens is associated with unfavourable clinicoprognostic factors in B-cell chronic lymphocytic leukaemia.

The cross-lineage expression of five myelomonocytic antigens (CD11b, CD11c, CD13, CD14, and CD15) was analysed in neoplastic lymphocytes from 100 consecutive B-cell chronic lymphocytic leukaemia (B-CLL) patients. CD14 antigen was detected on lymphocytes from more than 50% of patients whilst smaller percentages of samples were positive for CD11b (21%), CD11c (26%), CD13 (22%), and CD15 (7%). The presence of the CD13 antigen on neoplastic lymphocytes showed a statistically significant association with the two most important unfavourable clinicoprognostic factors in B-CLL: advanced clinical stage (CD13, P less than 0.01 by the Rai staging system; P less than 0.05 by the Binet staging system) and the diffuse pattern of bone marrow infiltration (CD13, P less than 0.001). A multiple logistic regression analysis showed that the increased risk for CD13-positive patients (13.7-fold higher than CD13-negative cases; P = 0.001) of presenting a diffuse pattern of bone marrow infiltration is independent of all other prognostic factors analysed including sex, age, lymphocyte counts, and clinical stage. A statistically significant association of CD11c (P = 0.002) and CD11b (P = 0.032) expression with the pattern of bone marrow infiltration was also found. Our results indicate for the first time a statistically significant association of CD13, CD11c, and CD11b antigens with unfavourable prognostic factors in B-CLL. They suggest that the cross-lineage expression of myeloid-associated surface peptidase (CD13-aminopeptidase N) and/or cell adhesion molecules (CD11c-LeuCAMc, CD11b-LeuCAMb) may influence the biological and clinical behaviour of chronic lymphoproliferative disorders of B cells.

Age Factors↗
PubMed1991

Endothelial-derived relaxing factor released by endothelial cells of human umbilical vessels and its impairment in pregnancy-induced hypertension.

The principal objective of this study was to determine and compare the capability of human umbilical vessels of normal and pregnancy-induced hypertensive parturients to produce and to release the endothelial-derived relaxing factor. A bolus of bradykinin injected in the perfusion system of human umbilical vessels induces a release of a relaxant factor, detectable by bioassay, that is pharmacologically similar to the endothelial-derived relaxing factor. Human umbilical cords were collected from normal and pregnancy-induced hypertensive parturients. In the latter group the release of endothelial-derived relaxing factor is extremely reduced. In fact, in umbilical vessels collected from normal parturients, bradykinin at a dose of 20 pmol produces a release of endothelial-derived relaxing factor equivalent to a relaxation induced by 59.9 +/- 11.0 and 30.8 +/- 11.4 pmol of glyceryl trinitrate for the artery and vein, respectively. The same dose of bradykinin in umbilical vessels, collected from pregnancy-induced hypertensive parturients, produces a release equivalent to 6.6 +/- 2.2 and 5.7 +/- 3.5 pmol of glyceryl trinitrate equivalent for the artery and vein, respectively. Neither an increasing bolus of exogenous bradykinin or an infusion of superoxide dismutase or L-arginine was able to restore the production of endothelial-derived relaxing factor to normal levels. Our results indicate a probable alteration of endothelial cell numbers or an alteration of the enzymatic pathway, probably due to cytotoxic endogenous factors produced in pregnancy.

Animals↗
PubMed1990

Differential expression of CD54/intercellular adhesion molecule-1 in myeloid leukemias and in lymphoproliferative disorders.

Indirect immunofluorescence staining with monoclonal antibody (MoAb) CL203.4 of malignant cells from 269 patients with hematologic malignancies showed a heterogeneous expression of CD54/intercellular adhesion molecule-1 (ICAM-1). This marker was expressed by malignant cells of 57 out of 118 patients with myeloid malignancies and 69 out of 135 with B-lymphoid malignancies. On the other hand, CD54 was not detected on malignant cells of 16 patients with T-lymphoid malignancies. In myeloid malignancies, CD54 is preferentially expressed by "stem cell-derived" malignancies, being detectable on blast cells from almost all patients affected by chronic myelogenous leukemia in blast phase or myelodysplastic syndromes and by only 34% of patients with de novo acute myeloid leukemia (AML). The expression of CD54 did not correlate with any specific myeloid FAB subtype, although three cases of highly undifferentiated AML (FAB MO) displayed maximal levels of the antigen. The expression of CD54 in AML was significantly associated with that of CD34 and HLA-DR antigens. In B-lymphoid malignancies, CD54 expression appears to correlate with the differentiation stage of malignant cells, since B-origin acute lymphoblastic leukemias and conventional B-chronic lymphocytic leukemias (B-CLL; ie, "dim SIg" CLL) expressed lower levels of CD54 than more mature lymphoproliferative disorders ("bright SIg" CLL, prolymphocytic leukemias, and lymphoplasmacytic tumors). "High-grade" B-cell non-Hodgkin's lymphomas (B-NHL) express in general a higher level of CD54 than "low-grade" ones. This finding in conjunction with the expression of CD54 in all 17 patients with "bright SIg" CLL investigated (characterized by marked organomegaly and poor prognosis) suggest that the differential expression of CD54 in lymphoproliferative disorders may also relate to their degree of malignancy.

Antigens, Surface↗
PubMed1990

Report of an unusual small lymphocytic B-cell lymphoma selectively involving the B-zone of lymph node.

Selective involvement of the B-cell compartment of lymph node by B-cell malignant lymphomas is an occasional finding related to early phases of lymph node infiltration. The authors have observed a unique case of diffuse small lymphocytic lymphoma that consisted of immunohistologically and genotypically proven B-clonal population exhibiting a repetitive pattern of infiltration in three lymph node samples obtained from the patient during a 9-year period. This pattern consisted of a selective and complete replacement of the B-areas with disappearance of follicles and widening of the medullary cords, an expanded T-zone showing features consistent with dermatopathic lymphadenitis and well-preserved sinuses. Clinically, multiple involved sites at presentation (lymph nodes, spleen, skin, bone marrow, and peripheral blood) and during the 9-year follow-up (testis) were detected, and the disease was associated with a relative indolent course like other low-grade lymphomas. The phenotypic profile of lymphoma cells studied by immunoperoxidase method, and by single-labeling and double-labeling flow cytometric analyses (SIg+, K+, LN2+, MB1+, MB2+, HLA-DR+, CD 9+, CD19+, CD 20+, CD 21+, CD 22+, CD 24+, Leu 8+, CD 5-, CD 10-, CD 11b-, CD 11c-, CD 25-, CD 38-, PCA-1-, FMC-7-, CD 23-) was consistent with a B-cell proliferation at an intermediate stage of differentiation but distinct from other well-defined B-cell neoplasms. Whether such unique B-zone pattern was due to an intrinsic property of this lymphoma or it is to be related to the coexisting reactive T-zone expansion remains controversial.

Antibodies, Monoclonal↗