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Biomedical subjects

S Morelli

Publications and source records attributed to S Morelli.

At least 91 records · Page 5Linked to original sources
PubMed1993

Interleukin-3 in vivo: kinetic of response of target cells.

Human recombinant interleukin-3 (IL-3; Sandoz AG, Basel, Switzerland) was administered for 7 days to patients with neoplastic disease and normal hematopoiesis. The purpose of the study was to assess IL-3 toxicity, to identify target cells, to define their kinetics of response at different dose levels, and to determine if IL-3 in vivo increased the sensitivity of bone marrow (BM) progenitors to the action of other hematopoietic growth factors. A total of 21 patients entered the study; the dosage ranged from 0.25 to 10 micrograms/kg/d. The effect on peripheral blood cells during treatment showed no significant changes in the number of platelets, erythrocytes, neutrophils, or lymphocytes (and their subsets). A mild monocytosis and basophilia occurred. Eosinopenia, present in the first hours of treatment, was followed by a dose-and time-dependent eosinophilia. IL-3 treatment affected BM cell proliferation by increasing the percentage of BM progenitors engaged in the S-phase of the cell cycle. The effect was dose dependent, with the various progenitors showing different degrees of sensitivity. The most sensitive progenitors were the megakaryocyte progenitors (colony-forming unit-megakaryocyte), then the erythroid progenitors (burst-forming unit-erythroid), and finally the granulo-monocyte progenitors (colony-forming unit-granulocyte-macrophage) whose proliferative activity was stimulated at the higher doses of IL-3. Only a slight increase in the proliferative activity of myeloblasts, promyelocytes, and myelocytes was observed, whereas the activity of erythroblasts was unchanged. The priming effect was such that BM progenitors, purified from patients treated with IL-3, produced more colonies in vitro in the presence of granulocyte colony-stimulating factor (G-CSF; granulocyte colonies), IL-5 (eosinophil colonies), and granulocyte-macrophage CSF (GM-CSF; predominantly eosinophil colonies). These data indicate that even in vivo IL-3 acts essentially as a primer for the action of other cytokines. Therefore, optimum stimulus of myelopoiesis will require either endogenous or exogenous late-acting cytokines such as G-CSF, erythropoietin, GM-CSF, and IL-6 for achieving fully mature cells in peripheral blood. If exogenous cytokines are used with IL-3, it is likely that G-CSF will yield more neutrophils, whereas GM-CSF may enhance eosinophils, monocytes, and neutrophils. Attention to the clinical relevance of each cell type will be necessary and should determine the selection of the combination of cytokines.

Adult↗
PubMed1993

Generation of inositol phosphates, diacylglycerol and calcium fluxes in myoblasts treated with 1,25-dihydroxyvitamin D3.

We have examined the effects of the seco-steroid hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on membrane phosphoinositide metabolism, protein kinase C (PKC) activation and influx of extracellular Ca2+ in chick-embryo muscle-cell (myoblast) cultures. At physiological concentrations, the hormone induces a rapid (15 s) and transient release of inositol triphosphate (InsP3) and diacylglycerol (DAG). InsP3 release is maximal at 60 s (80% above controls) and then declines. The effects of 1,25(OH)2D3 on InsP3 production exhibited specificity, as 25-hydroxy-vitamin D3 and 24,25-dihydroxy-vitamin D3 did not alter myoblast InsP3 levels. The stimulation of DAG is biphasic, with peaks at 60 s (+105%) and 5 min (+700%). The second phase of DAG release is not associated with changes in InsP3. 1,25(OH)2D3 induces a rapid (within 60 s) accumulation of InsP2, and its effect on InsP is delayed (120 s). The hormone rapidly activates myoblast PKC, with maximal translocation of activity from the cytosol to the cell membrane occurring at 60 s. Myoblast 45Ca uptake significantly increases within 30 s of exposure to 1,25(OH)2D3. The response is time- (0.5-10 min) and dose- (1 pM-10 nM) dependent. The effects of the hormone are mimicked by the Ca(2+)-channel agonist Bay K 8644 and are effectively suppressed by nifedipine and extracellular EGTA. The results suggest that the rapid non-genomic actions of 1,25(OH)2D3 in myoblasts involve second-messenger systems associated with the generation of InsP3 and DAG and regulation of Ca2+ fluxes through voltage-operated channels.

Animals↗
PubMed1993

Granulocyte-macrophage colony stimulating factor and interleukin 3: target cells and kinetics of response in vivo.

Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3) target cells have been studied in vivo in subjects with normal hemopoiesis. GM-CSF administration elicits a rapid and sustained neutrophilia, monocytosis and eosinophilia due to a direct proliferative stimulus on all progenitors and precursors of the granulomonopoietic lineage. GM-CSF is also a powerful stimulator of erythroid burst forming unit (BFU-E) and megakaryocyte colony forming unit (CFU-MK) proliferation. Its action, however, does not extend to more mature erythroid and megakaryocyte cells suggesting the need for combined treatment with lineage-specific growth factors such as erythropoietin (Epo) or IL-6 to obtain a complete myeloid stimulation. When GM-CSF is discontinued, its action rapidly vanishes, and a rapid decline in the proliferative rate of target cells to values below the initial ones occurs. The potential clinical usefulness of this phenomenon in regard to cancer chemotherapy is discussed. IL-3 treatment induces only a rapid and marked eosinophilia. Chronic IL-3 administration, however, increases the proliferation of all myelopoietic progenitors and primes CFU-GM to become more sensitive in vitro to the action of granulocyte CSF (G-CSF), GM-CSF and IL-5. Whereas an increased IL-5 sensitivity seems devoid of therapeutic potential, the priming of G-CSF and GM-CSF action suggests rational scheduling for a combined treatment of IL-3 with other hemopoietic growth factors.

Animals↗
PubMed1993

Evidence for the participation of protein kinase C and 3',5'-cyclic AMP-dependent protein kinase in the stimulation of muscle cell proliferation by 1,25-dihydroxy-vitamin D3.

Treatment with 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) (1-12 h, 10(-10) M) stimulates DNA synthesis in proliferating myoblasts, with an early response at 2-4 h of treatment followed by a maximal effect at 10 h. To investigate the mechanism involved in the mitogenic action of the hormone we studied the possible activation of intracellular messengers by 1,25(OH)2D3. The initial phase of stimulation of [3H]thymidine incorporation into DNA by the sterol was mimicked by the protein kinase C activator tetradecanoylphorbol acetate (TPA) in a manner which was dose dependent and specific as the inactive analog 4 alpha-phorbol was without effect. Maximal responses to TPA (100 nM) were obtained at 4 h. Staurosporine, a protein kinase C inhibitor, blocked the effect of 1,25(OH)2D3 on myoblast proliferation at 4 h. In addition, a fast (1-5 min) elevation of diacylglycerol levels and membrane-associated protein kinase C activity was observed in response to 1,25(OH)2D3. The adenylate cyclase activator forskolin (20 microM) and dibutyryl-cAMP (50 microM) increased DNA synthesis reproducing the second 1,25(OH)2D3-dependent stimulatory phase at 10 h. Inhibitors of protein kinase A blocked the increase in muscle cell DNA synthesis induced by 1,25(OH)2D3 at 10 h. Significant increases in cyclic AMP levels were detected in myoblasts treated with the sterol for 1-10 h. The calcium channel antagonist nifedipine (5-10 microM) abolished both the effects of 4-h treatment with 1,25(OH)2D3 or TPA and 10-h treatment with 1,25(OH)2D3 or dibutyryl-cAMP. Similar to the calcium channel agonist Bay K8644, 1,25(OH)2D3 stimulated myoblast 45Ca uptake and its effects were blocked by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Oligonucleotide degradation contributes to resistance to antisense compounds.

A subline of the human B cell lymphoma DHL-4, grown in the artificial serum-free medium HB101, displayed a resistant phenotype to the activity of an antisense oligodeoxynucleotide (aODN) effective on the parental DHL-4 line. It was found that the cellular uptake of the 18mer aODN in the two cell lines was almost the same. In contrast, the unresponsive subline DHL-4r degraded the aODN very efficiently, in contrast to the stability of aODN inside cells of the parental DHL-4 line. Activation of the degrading 'machinery' combined with selective properties of the artificial medium may be responsible for the loss of responsiveness to aODN.

Antineoplastic Agents↗
PubMed1993

Pulmonary arterial hypertension responsive to immunosuppressive therapy in systemic lupus erythematosus.

Two female patients with recent diagnosis of systemic lupus erythematosus (SLE) are reported. Pulmonary arterial hypertension was diagnosed by Doppler echocardiography. Immunosuppressive therapy was started at the time of diagnosis of SLE. After 2 months of therapy, Doppler echocardiography was repeated and the estimated pulmonary artery systolic pressure was substantially decreased from 78 to 42 mmHg and from 67 to 42 mmHg, respectively, along with significant improvement of the clinical conditions.

Adult↗
PubMed1993

[Pulmonary hypertension and systemic sclerosis].

BACKGROUND: Pulmonary involvement in systemic sclerosis (SS) is a frequent complication and is associated with a poor prognosis. Pulmonary hypertension may or may not develop, however, its recognition is usually possible only in advanced stages. METHODS: In this study we noninvasively evaluated the pulmonary artery systolic pressure in 31 patients with SS using Doppler echocardiography. Pulmonary hypertension was detected in 48.4% of the patients. RESULTS: The prevalence of pulmonary hypertension was similar in patients with limited SS and diffuse SS (42.9% and 52.9%, respectively; p = NS). No differences were observed in pulmonary artery systolic pressure between patients with limited or diffuse SS and pulmonary hypertension. Pulmonary hypertension was usually mild, and only in two cases was pulmonary systolic pressure higher than 50 mmHg (63 and 107 mmHg, respectively). CONCLUSIONS: Pulmonary hypertension is frequently observed in patients with SS. The patients with diffuse or limited SS are equally affected by this complication. Doppler echocardiography has proved to be the technique of choice for the evaluation of pulmonary involvement in patients with SS because it is noninvasive, inexpensive and allows serial examinations. Early recognition of pulmonary hypertension may favor the use of therapeutical strategies to prevent the progression to advanced forms.

Adult↗
PubMed1992

Enhanced release of atrial natriuretic factor during exercise-induced myocardial ischaemia in patients after acute myocardial infarction.

To determine whether acute myocardial ischaemia induced by dynamic exercise can lead to changes in plasma levels of atrial natriuretic factor, we performed symptom-limited bicycle electrocardiographic tests in 20 males with recent acute myocardial infarction and in 8 control males. Ten patients developed exercise-induced myocardial ischaemia and 10 patients did not. There were no significant differences between the two groups with regard to age, site of myocardial infarction, urinary sodium, atrial sizes, radionuclide left ventricular ejection fraction, workload, baseline and peak-exercise heart rate, baseline and peak-exercise rate-pressure product, duration of exercise. Also baseline atrial natriuretic factor concentrations were similar in both groups (ischaemic patients: 34.51 +/- 15.73 pg/ml; nonischaemic patients: 27.17 +/- 8.74 pg/ml, NS), while peak-exercise atrial natriuretic factor concentrations were higher in patients with exercise-induced myocardial ischaemia (112.31 +/- 35.5 pg/ml) than in the others (80.46 +/- 23.43 pg/ml) (P less than 0.05). After 15 minutes of recovery, plasma atrial natriuretic factor levels were still raised only in the ischaemic patients (63.3 +/- 15.44 pg/ml, P less than 0.01), returning to baseline after 30 minutes in both groups. In control subjects, the behaviour of atrial natriuretic factor resembled that of the patients without exercise-induced ischaemia, with a significant increase at peak-exercise (from baseline levels of 23.1 +/- 10.5 pg/ml to peak-exercise levels of 91.3 +/- 14.5 pg/ml, P less than 0.0005) and a rapid return to baseline levels after 15 minutes of recovery (28.5 +/- 10.6 pg/ml, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

In vivo effect of human granulocyte-macrophage colony-stimulating factor on megakaryocytopoiesis.

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on megakaryocytopoiesis and platelet production was investigated in patients with normal hematopoiesis. Three findings indicated that GM-CSF plays a role in megakaryocytopoiesis. During treatment with GM-CSF (recombinant mammalian, glycosylated; Sandoz/Schering-Plough, 5.5 micrograms protein/kg/d, subcutaneously for 3 days) the percentage of megakaryocyte progenitors (megakaryocyte colony forming unit [CFU-Mk]) in S phase (evaluated by the suicide technique with high 3H-Tdr doses) increased from 31% +/- 16% to 88% +/- 11%; and the maturation profile of megakaryocytes was modified, with a relative increase in more immature stage I-III forms. Moreover, by autoradiography (after incubation of marrow cells with 125I-labeled GM-CSF) specific GM-CSF receptors were detectable on megakaryocytes. Nevertheless, the proliferative stimulus induced on the progenitors was not accompanied by enhanced platelet production (by contrast with the marked granulomonocytosis). It may be suggested that other cytokines are involved in the regulation of the intermediate and terminal stages of megakaryocytopoiesis in vivo and that their intervention is an essential prerequisite to turn the GM-CSF-induced proliferative stimulus into enhanced platelet production.

Cell Differentiation↗
PubMed1991

Early hepatitis during intravenous amiodarone administration.

Two patients with acute changes suggesting acute hepatitis after parenteral amiodarone administration are described. No other explanation for liver damage was found in these patients. Normalization of liver function in spite of continuation of drug infusion was observed.

Aged↗
PubMed1990

Opposite effect of tumor necrosis factor alpha on granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor-dependent growth of normal and leukemic hemopoietic progenitors.

The effect of recombinant human tumor necrosis factor alpha (TNF-alpha) on normal and chronic myeloid leukemia granulocyte-macrophage progenitors (CFU-GM) growing in semisolid agar cultures in the presence of recombinant granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor was studied. Granulocyte-macrophage colony-stimulating factor-dependent growth of normal and chronic myeloid leukemia bone marrow CFU-GM was greatly enhanced by TNF-alpha at doses of 0.1 to 100 units/ml. Growth enhancement included neutrophil, eosinophil, and monocyte-macrophage colonies and clusters at 7 and 14 days of culture. Since similar results were achieved with highly enriched progenitor cell populations, devoid of accessory cells, an indirect effect on CFU-GM growth through the release by accessory cells of other cytokines upon TNF-alpha stimulation was thus ruled out. By contrast, the same doses of TNF-alpha inhibited the growth of normal CFU-GM in granulocyte colony-stimulating factor-dependent cultures. Taken together, our findings indicate that the final effect of TNF-alpha on normal bone marrow granulocyte-macrophage progenitor growth is dependent on the specific growth factor interacting with it, and that both normal and chronic myeloid leukemia CFU-GM are equally responsive to the combined effects of TNF-alpha and a given colony-stimulating factor.

Bone Marrow↗
PubMed1990

[Monitoring of respiratory exchange during ergometric test in patients with heart failure: current aspects and prospects].

The current techniques of respiratory gas-exchange monitoring during stress testing in patients with congestive heart failure have provided new physiopathologic and clinical data. The "breath-by-breath" measurement of oxygen consumption and carbon dioxide production and the evaluation of the relationship between these parameters and respiratory volumes, allow to determine both ventilatory and metabolic responses during exercise, thus giving a precise estimate of the effective cardiopulmonary functional capacity. The demonstration of peripheral vascular and metabolic abnormalities by these techniques have provided new insights into the mechanism of dyspnea and fatigue in patients with heart failure. Although the relationship between respiratory and metabolic parameters and hemodynamics has been extensively studied, its mechanisms are still unclear. Moreover, controversy still exists as to the link between functional capacity and prognosis. Finally, recent studies on the cardiopulmonary adaptations to exercise training in patients with left ventricular dysfunction, have clearly demonstrated clinical and hemodynamic improvement after conditioning. These data, if confirmed, may provide a new approach in the management of patients with this disorder.

Anaerobic Threshold↗
PubMed1989

A case control study for major trauma in geriatric patients.

This study analyzed age as a univariate factor in survival in a national group of 46,613 major trauma patients and compared 180 elderly major trauma patients (greater than or equal to 65 years) to a similarly injured group of 3,918 younger patients (less than 65 years). In the national group, mortality rose sharply between age 45 (10%) and 55 (15%) and doubled at age 75 years (20%). This age-dependent survival decrement occurred at all Injury Severity Score values, for all mechanisms of injury, and for all body regions. In the comparison study, mortality in the elderly group was nearly double that of mortality in the younger group (27% vs. 14%). The older patients had a markedly higher complication death rate, especially for pulmonary (14/100 vs. 6.1/1100) and infectious complications (4.6/100 vs. 0.7/100). The median length of stay was twice as long for the older patients (14 days vs. 7 days). Cost data showed that the DRG prospective payment system grossly underestimated the cost of care for these patients (mean loss of $2,177.14 per patient). To minimize mortality and morbidity, triaging elderly trauma victims to trauma centers at a much lower threshold than similarly injured younger patients is recommended. The current DRG system should be altered to account for age-dependent morbidity. Further study is needed to determine whether more rigorous infection prophylaxis, immunomodulation, and pulmonary therapy will augment survival in elderly patients.

Adolescent↗
PubMed1989

[Holiday heart syndrome: spontaneous reversibility of the electrocardiographic and echocardiographic alterations].

The holiday heart syndrome is characterized by symptomatic arrhythmias more often supraventricular, elicited by alcohol ingestion, typically during the week-end period. After admission, electrocardiographic changes, which disappear in few days, are often reported. A case of an alcoholic with syncopal episodes related to alcohol ingestion is described. In this patient, remarkable changes of ventricular repolarization on the electrocardiogram associated with impairment of ventricular diastolic function on the Doppler echocardiographic study are showed. ECG and echo-Doppler data reversed to normality after few days of alcohol withdrawal.

Alcoholism↗
PubMed1983

Avulsion of the scalp treated by microvascular repair: the use of leeches for post-operative decongestion.

A 28-year-old fitter and turner was scalped at work. The scalp was avulsed from the nuchal area to the eyebrows in one piece. It was successfully replanted by microvascular surgery. Leeches were used to decongest the flap when venous drainage appeared inadequate during the first week. Only a small part of the flap eventually failed to survive and normal hair growth returned in all other areas.

Accidents, Occupational↗