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Biomedical subjects

L Moretti

Publications and source records attributed to L Moretti.

At least 55 records · Page 3Linked to original sources

[Enalapril and acebutolol in essential arterial hypertension. Comparison of the 2 drugs and evaluation of their combination].

The effects of a mid-term antihypertensive treatment with Acebutolol (A) 400 mg once-daily alone, Enalapril (E) 20 mg once-daily alone and their combination (A + E) in 12 hypertensive patients (pts.) have been evaluated. The diastolic (DBP) and systolic (SBP) blood pressure values have been evaluated in supine and upright position and at the end of an exercise test. Basic values obtained after 3 weeks of treatment with placebo have been matched with values observed after 3 months of each treatment (A; A + E; E). In order to evaluate the effectiveness of the combination, pts. were divided into two groups: the first group was given A, than A + E and finally E; in the second group the order was reversed. Our findings showed a more significant reduction of DBP in supine and upright position and after exercise (p less than .05) and of SBP in supine and upright position (p less than .05) after treatment with E. The addition of A to E did not produce a further significant reduction in blood pressure values except after exercise (p less than .01).

Acebutolol↗

Effects of treating marrow with a CD3-specific immunotoxin for prevention of acute graft-versus-host disease.

Data from human clinical trials and animal experiments have suggested that T lymphocytes in donor marrow help to facilitate engraftment after allogeneic bone marrow transplantation, possibly through a suppressive effect on the immunity of the recipient. In previous studies marrows from HLA-identical donors were treated ex vivo with a mixture of eight monoclonal antibodies together with rabbit complement to achieve a 3-log depletion of T cells and CD3-negative lymphoid cells. Transplantation of this marrow was associated with a 27% actuarial risk of graft failure in leukemic recipients conditioned with cyclophosphamide (120 mg/kg) and 15.75 Gy fractionated total body irradiation. In the present study, we employed an anti-CD3 ricin A-chain-containing immunotoxin (64.1-A) together with 20 mM NH4Cl to achieve a selective 3-log depletion of CD3-positive cells. The patient entry criteria and pretransplant conditioning regimen were identical to those used in previous studies. Despite the differences in marrow treatment, the clinical outcome of the present study was similar to that obtained previously. Graft-versus-host disease (GVHD) was largely prevented without the need for post-transplant immunosuppression, but two of the eight patients developed graft failure. These results indicate that CD3-negative cells have little or no ability to initiate GVHD. To the extent that graft failure in this study was not caused by stem cell damage or loss of CD3-negative cells during ex vivo processing of the marrow, it appears that the lymphoid cells required for facilitating allogeneic engraftment under these conditions are CD3-positive.

Adult↗

Expression of c-myb protooncogene and other cell cycle-related genes in normal and neoplastic human colonic mucosa.

The expression of c-myb, c-myc, histone H3, and ornithine decarboxylase genes was examined by Northern blot analysis in the normal and neoplastic mucosa of ten subjects affected by colon cancer. The mRNA levels of c-myb protooncogene were detected at low levels in all normal samples but were increased in the neoplastic mucosa of six cases in comparison to the normal counterpart. In five of these six cases the mRNA levels of c-myc, histone H3, and ornithine decarboxylase mRNAs were also increased, suggesting that there is a relation between the high expression of c-myb and the fraction of cycling neoplastic cells.

Cell Cycle↗

Cellular levels of mRNA from c-myc, c-myb and c-fes onc-genes in normal myeloid and erythroid precursors of human bone marrow: an in situ hybridization study.

The expression of three onc-genes, c-myc, c-myb and c-fes, has been evaluated at the cellular level in myeloid and erythroid precursors of normal human bone marrow, by "in situ" hybridization with tritium-labelled probes. A relatively large amount of m-RNA from the three onc-genes was detected in myeloblasts and promyelocytes, but whereas the expression of c-myc and c-myb decreased in more advanced stage of maturation of the myeloid lineage, c-fes mRNA remained at a relatively high level until the granulocyte stage. c-myc and c-myb were expressed at a fairly high level in basophilic erythroblasts, which also showed low levels of c-fes mRNA. No expression of these onc-genes was detectable in more mature erythroblasts. Megakaryocytes showed high levels of m-RNA from all three onc-genes. Our results suggest that c-myc and c-myb expression is related in some way to the cellular proliferation of myeloid and erythroid precursors, whereas c-fes expression is more restricted to myeloid differentiation.

Bone Marrow Cells↗

Study of the levels of expression of two oncogenes, c-myc and c-myb, in acute and chronic leukemias of both lymphoid and myeloid lineage.

Total cellular RNA from a series of leukemic cell populations, both myeloid and lymphoid, as well as from normal circulating lymphocytes was analysed for the expression of two cellular oncogenes, c-myc and c-myb, by Northern blot hybridization assay. Expression of c-myc but not of c-myb was observed in unstimulated normal lymphocytes. Stimulation by PHA was shown to activate the expression of both genes. Remarkably different levels of expression of c-myc were observed in ALL, whereas in CLL the expression of c-myc was uniformly low or absent. Differential expression of c-myc was detected in AML as well as in CML, c-myb was differentially expressed in AML and ALL, and absent in CLL and CML. Other single cases of hemopoietic disorders were studied, but the expression of the two oncogenes was low or absent. Neither evident genome amplification nor genome rearrangements were detected in the cell DNAs digested with restriction endonucleases.

DNA, Neoplasm↗

Expression of human c-fes onc-gene occurs at detectable levels in myeloid but not in lymphoid cell populations.

Total cellular RNA from a variety of myeloid and lymphoid cell populations, normal and leukaemic, was analysed for the expression of a human cellular onc-gene, c-fes, by northern blot hybridization assays. The probe used was a molecularly cloned human DNA sequence homologous to the 5' terminal sequence of v-fes. All the myeloid cellular populations expressed the c-fes gene. In some cell populations at an advanced stage of differentiation (circulating leucocytes from Chronic myeloid leukaemia (CML), HL60 cells induced to differentiate by retinoic acid) the level of expression was even higher than in early stages of the myeloid lineage (blast cells from AML, uninduced HL60 cells). No transcript of the c-fes gene was detected in the different lymphoid populations studied. The occurrence of an RNA complementary to the c-fes sequence appears sufficiently characteristic of a myeloid population to distinguish it from a lymphoid population, normal and leukaemic.

Cell Differentiation↗

Activation of c-myb expression by phytohemagglutinin stimulation in normal human T lymphocytes.

The expression of c-myb in normal human T lymphocytes directly derived from a normal subject and not adapted to continuous growth in culture was found to be markedly increased after phytohemagglutinin stimulation. In the same cells, the expression of c-myc mRNA is a much earlier event compared with the appearance of c-myb mRNA, which takes place soon after that of histone H3 mRNA. The increase in c-myb expression was not due to a particular T-lymphocyte subset, as shown by in situ hybridization assays.

Cells, Cultured↗

The use of retinal fluorangiography techniques in the study of cerebral circulation.

Retinal fluorangiographic techniques can be employed in the study of cerebrovascular disorders in relation to the embryological, anatomic and functional affinities between the cerebral and retinal circulation. The techniques currently used have been improved by means of the computer analysis of the photographic image, thus allowing qualitative evaluations of the vascular dynamics and quantitative evaluations referred to remarkable variations. These improved techniques can be summed up as follows: equidensitometry with arbitrary colors, computerized fluorangiography for the evaluation of the vascular caliber, computer analysis of mean transit time (m.t.t.). A new type of qualitative evaluation not considering the fluorangiographic image has recently been introduced: the fluorophotometric analysis.

Adult↗

[Identification of patients with stenosis of the main trunk of the left coronary artery by ergometric variables].

In 354 patients with coronary artery disease (9 with greater than or equal to 90%, 42 with 50-75% and 303 with no left main (LM) stenosis, prevalence of ergometric criteria of severe disease was considered. In patients with LM stenosis were more frequent: work load less than or equal to 75 watt (p less than 0,001); ST depression greater than 2 mm (p less than 0,01); 3 or more leads involved (p less than 0,05); no increment of heart rate (p less than 0,01) or of blood pressure (p less than 0.01). Work load had the best predictive value (30%) of LM stenosis, associated with a reasonable sensitivity (55%). Combination ST depression + heart rate or work load + blood pressure had a predictive value of 100%, but minimal sensitivity (8%). In detecting greater than or equal to 90% LM stenosis heart rate had the best predictive value (13%), associated with high sensitivity (78%). Presence of 2 any criteria could detect all greater than or equal to 90% LM stenosis (sensitivity 100%, predictive value 11%). ST depression + heart rate had a predictive value of 100% and a sensitivity of 44%. It is concluded that no single or associated exercise variable has both high sensitivity and high predictive value of LM stenosis.

Adult↗

Sequence complexity and diversity of polyadenylated RNA molecules transcribed in human myeloid cells. Leukemic myeloblasts and HL60 promyelocytes uninduced and induced to terminal differentiation with retinoic acid.

The kinetic composition of the polyadenylated RNAs of leukemic myeloblasts and HL60 promyelocytes was examined by the cDNA-poly (A) +RNA reassociation technique before and after the induction of differentiation with retinoic acid. The data obtained in the homologous hybridizations show the following main features: the sequence complexity of the total poly(A) +RNA molecules is 72,000 different sequences in leukemic myeloblasts, 64,000 in HL60 promyelocytes before induction and 26,000 after treatment of HL60 with retinoic acid; the number of sequences reacting as abundant is clearly higher in HL60 promyelocytes (5,000) than in leukemic myeloblasts (1,000), and the number decreases sharply after induction (300); the repetition frequency of the abundant and rare components is almost unchanged between leukemic myeloblasts and HL60 promyelocytes, while it is markedly increased after induction with retinoic acid. The heterologous reactions show that the observed differences in complexity are mainly related to the missing of rare sequences. Moreover, an important portion of sequences already present in leukemic myeloblasts has a definitely higher repetition frequency in HL60 promyelocytes. Finally, the most abundant sequences in HL60 cells after induction are already present before treatment. The data presented here suggest that, during human myeloid differentiation, important, possibly transcriptional, regulatory mechanisms of gene expression are active long after the first commitment event of the hemopoietic undifferentiated stem cell.

Adult↗

[The pressure-dimension curve and midwall stress. Use of a combined hemodynamic-echocardiographic method and correlation with contrast ventriculography].

An invasive (left ventricular pressure recording) and a noninvasive technique (M-mode echocardiography) were combined during the hemodynamic study of 15 patients with various degrees of left ventricular impairment, in order to provide left ventricular function parameters independent from contrast studies. Left ventricular pressure, dimension and wall thickness changes were continuously digitized on a computer system, which was able to derive the ventricular pressure-dimension loop and to calculate the midwall equatorial stress at end-diastole and peak-systole. The parameters derived from the loop (diastolic work, net systolic work, cycle efficiency) and midwall meridional and circumferential stresses were compared with the results of contrast ventriculography and with the wall hypertrophy index. Diastolic work appeared to be correlated with the systo-diastolic volume change; systolic work correlated with the ejection fraction; the cycle efficiency was inversely correlated with both end-diastolic and end-systolic volumes and directly correlated with the hypertrophy index. Midwall stress, both end-diastolic and peak-systolic, was strongly and positively correlated with ventricular volumes, while it decreased with increasing hypertrophy. Systolic stress increased with decreasing ejection fraction. The combined echo-pressure technique, through the evaluation of the pressure-dimension loop and the calculation of wall stress, can generate data of left ventricular function that allow a more complete assessment of left ventricular impairment.

Adolescent↗

Allogeneic marrow transplantation for thalassemia.

Thirteen patients with homozygous beta thalassemia underwent allogeneic marrow transplantation from sibling donors, 12 of whom were heterozygous for beta thalassemia. Six patients were transplanted in an advanced stage of their disease while seven were transplanted early in their disease course. Donors and recipients were genotypically identical for the HLA-A, -B and -D loci in 11 cases and mismatched for the D locus in two. A variety of preparative regimens was utilized involving high doses of busulphan (Bu) and/or cyclophosphamide (CY) and/or total body irradiation (TBI). Failure of engraftment or autologous hematologic recovery after transient engraftment was seen after intensive preparative regimens including: CY 200 mg/kg and 800 rad of TBI; Bu 8 mg/kg and CY 200 mg/kg; and Bu 8 mg/kg, CY 200 mg/kg, and 300 rad of TBI. A regimen of Bu 16 mg/kg, CY 200 mg/kg, and 400 rad of TBI resulted in deaths from transplant-related causes in the three patients treated with this regimen. Seven of the 13 patients are surviving 363-665 days after transplant. Five of the seven failed to achieve engraftment or had autologous reconstitution after transient engraftment. Five of the six deaths were transplant related, and one patient died of cardiac failure one year after an unsuccessful transplant attempt. Two patients are surviving with engraftment and without thalassemia major 363 and 491 days after transplantation. Both of these patients were transplanted early in their disease course.

Adolescent↗

Histomorphologic study of bone marrow in acute leukemia following chemotherapy and autologous bone marrow transplantation.

Twenty-six patients with acute myeloid leukemia, acute lymphoid leukemia and chronic granulocytic leukemia in blast crisis were studied by means of multiple biopsies during a polychemotherapeutic or autologous bone marrow transplant protocol. Following chemotherapy, 3 main phases were observed: leukemic cellular depletion, stromal bone marrow reconstruction, and bone marrow hemopoietic restoration. Following intensive chemotherapy (in 2 patients after cyclophosphamide and total body irradiation) and autologous bone marrow transplantation, the 3 phases appeared to be shorter. A focal or diffuse increase in marrow fibrosis was a common finding in leukemia. An effective antileukemic therapy resulted in a decrease in fibrosis, whereas in some cases a further increase was a precocious sign of leukemia relapse.

Adolescent↗

Ontogeny of granulocyte-macrophage progenitor cells in the human fetus.

The CFU-Gm content of liver, spleen and bone marrow of human fetuses was determined from the 8th to 28th week of gestational age. The study of progenitor cells from 43 fetal livers revealed that the CFU-Gm increased from 8 to 12 weeks, was relatively stable through 16 weeks and thereafter declined by 22 to 24 weeks. The total number of liver CFU-Gm rose from 10(4) to greater than 10(6) CFU-Gm by the 16th week of gestation and declined to approximately 4 X 10(5) progenitor cells by 22 to 24 weeks. Peak values of bone marrow CFU-Gm were noted at 10 to 14 weeks of gestation. Generally, the numbers of these progenitor cells declined by 16 to 18 weeks; however, several high values were obtained at later times. Splenic CFU-Gm were relatively constant in number between 12 and 28 weeks of gestation with no correlation with fetal age. Thus, these studies indicate that certain fetal tissues contain substantial numbers of hemopoietic progenitor cells. Based on the quantity of CFU-Gm obtained, it appears feasible to use fetal liver cells as a source of progenitor cells for transplantation.

Bone Marrow↗