PubMed Health⌕ Search

Biomedical subjects

S Pepe

Publications and source records attributed to S Pepe.

At least 91 records · Page 5Linked to original sources
PubMed1991

Cooperative effect of 8-Cl-cAMP and rhGM-CSF on the differentiation of HL-60 human leukemia cells.

In HL-60 leukemia cells the site-selective cAMP analog, 8-Cl-cAMP, at a dose of 5 microM produced growth inhibition with no signs of toxicity, whereas granulocyte-macrophage colony stimulating factor (GM-CSF) exerted an early transient increase of cell proliferation which was followed by differentiation toward monocytes. 8-Cl-cAMP in combination with GM-CSF blocked the growth stimulation due to GM-CSF and demonstrated a synergistic effect on the differentiation of HL-60 cells. The early proliferative effect of GM-CSF was correlated with an increased expression of type I regulatory subunit of cAMP-dependent protein kinase (RI alpha). Treatment with an RI alpha antisense oligodeoxynucleotide suppressed the GM-CSF-inducible cell proliferation and differentiation. Conversely, an RII beta antisense oligodeoxynucleotide, which suppresses the RII beta and causes a compensatory increase in RI alpha level, greatly enhanced the early proliferative input and the differentiation induced by GM-CSF. These results provide an insight into the mechanism of action of GM-CSF and the rationale for a combination differentiation therapy with 8-Cl-cAMP and GM-CSF.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Differentiation of HL-60 leukemia by type I regulatory subunit antisense oligodeoxynucleotide of cAMP-dependent protein kinase.

A marked decrease in the type I cAMP-dependent protein kinase regulatory subunit (RI alpha) and an increase in the type II protein kinase regulatory subunit (RII beta) correlate with growth inhibition and differentiation induced in a variety of types of human cancer cells, in vitro and in vivo, by site-selective cAMP analogs. To directly determine whether RI alpha is a growth-inducing protein essential for neoplastic cell growth, human HL-60 promyelocytic leukemia cells were exposed to 21-mer RI alpha antisense oligodeoxynucleotide, and the effects on cell replication and differentiation were examined. The RI alpha antisense oligomer brought about growth inhibition and monocytic differentiation, bypassing the effects of an exogenous cAMP analog. These effects of RI alpha antisense oligodeoxynucleotide correlated with a decrease in RI alpha receptor and an increase in RII beta receptor level. The growth inhibition and differentiation were abolished, however, when these cells were exposed simultaneously to both RI alpha and RII beta antisense oligodeoxynucleotides. The RII beta antisense oligodeoxynucleotide alone has been previously shown to specifically block the differentiation inducible by cAMP analogs. These results provide direct evidence that RI alpha cAMP receptor plays a critical role in neoplastic cell growth and that cAMP receptor isoforms display specific roles in cAMP regulation of cell growth and differentiation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Suppression of malignancy targeting the intracellular signal transducing proteins of cAMP: the use of site-selective cAMP analogs, antisense strategy, and gene transfer.

An hypothesis has been presented suggesting that two isoforms of cAMP receptor proteins are crucial effectors in tumorigenesis. The evidence in support of this hypothesis shows that: (1) cAMP transduces dual controls, both positive and negative, on cell growth and differentiation. (2) Such dual controls are respectively governed by two isoforms of cAMP receptor proteins, the type I and type II regulatory subunits of cAMP-dependent protein kinase. (3) In normal physiology, the functional balance of these cAMP receptor isoforms is strictly controlled to meet either stimulation or inhibition of cell growth as it is required, whereas such control is lost in cancer cells. (4) Cancer cells can also be made to differentiate and acquire growth control when the functional balance of these intracellular signal transducers of cAMP is restored by the use of site-selective cAMP analogs, antisense strategy, or gene transfer, suggesting new approaches to cancer therapy.

Animals↗
PubMed1990

Regulation of the expression of the low-affinity IgE receptor (Fc epsilon RII) in the human monocyte-like cell line U-937 by phorbol esters and IgE.

The expression of the low-affinity receptor for IgE Fc epsilon RII) in the human monocyte-like U-937 cell line can be upregulated by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and by IgE. TPA induces terminal differentiation of U-937 cells and causes a four- to fivefold increase in the number of Fc epsilon RII. TPA also modulates the expression of several other membrane markers of U-937 cells. IgE alone has a modest effect on the expression of Fc epsilon RII (about a 10% increase), while simultaneous treatment of U-937 cells with TPA and IgE has a cooperative effect, causing an eightfold increase in the number of Fc epsilon RII. Cycloheximide strongly suppresses the expression of Fc epsilon RII, both in TPA-stimulated and unstimulated cells; this effect can be partly reversed by culturing the cells in the presence of IgE. These results suggest that TPA induces the expression of newly synthesized receptors, while IgE causes an accumulation of preformed receptors.

Antigens, CD↗
PubMed1990

[Validity of the use of penbutolol in essential arterial hypertension].

Thirty patients suffering from WHO I-II class slight-moderate essential arterial hypertension were treated with a beta-blocker (Penbutolol) alone and once a day to assess its antihypertensive effectiveness and its affect on heart frequency, lipid metabolism and kidney function. The drug proved highly effective in reducing P.A.S. and P.A.D. values and no negative influence was documented on lipid metabolism, kidney function or heart frequency.

Adult↗
PubMed1989

Flow cytometric analysis of DNA content in human ovarian cancers.

A total of 155 samples from 101 patients with ovarian cancer were investigated using flow cytometry to evaluate the DNA index and the percentage of cells in the various cell cycle phases. Thirty-four samples were DNA diploid tumours, while the other 121 were DNA aneuploid tumours. The DNA index was very stable in different sites and over time in the same patient. Tumour stage and ploidy were significantly associated: stages III and IV tumour stage were more likely to be DNA aneuploid. Patients with residual tumour size at first surgery greater than 2 cm had a significantly larger number of DNA aneuploid than DNA diploid tumours. The DNA index was also related to the degree of differentiation of the tumours. The percentage of cells in the S phase of the cell cycle was significantly higher in DNA aneuploid and in poorly differentiated tumours than DNA diploid and well differentiated tumours. Multivariate analysis using the Cox model showed that the DNA index and the percentage of cells in S phase were not independent prognostic variables in this study. Prospectively collected data should be accumulated before assigning the DNA index an important role as a biological prognostic factor in ovarian cancer.

DNA, Neoplasm↗
PubMed1988

Enhanced benzodiazepine responsiveness in rats with increased cholinergic function.

The effects of diazepam and muscimol on locomotor activity were examined in Flinders Sensitive Line (FSL) rats, derived by selective breeding methods from randomly bred Sprague-Dawley (RB) rats for increased behavioural and physiological sensitivity to the anticholinesterase, diisopropylfluorophosphate (DFP). Previous reports of increased behavioural sensitivity to oxotremorine, associated with increased striatal and hippocampal muscarinic receptor concentrations, were confirmed in FSL rats compared to RB rats. The FSL rats were more sensitive to the locomotor suppressant effects of diazepam and muscimol compared to RB. Binding experiments with [3H]-diazepam showed that FSL rats had an increased benzodiazepine receptor concentration in the striatum and hippocampus compared to Flinders Resistant Line rats (FRL). FRL did not differ significantly from RB in diazepam-induced changes in locomotor activity or the concentration of benzodiazepine receptors. No significant differences in the affinity of benzodiazepine receptors was detected between the three rat lines in the brain regions investigated. Thus FSL rats showed an increased behavioural sensitivity to both diazepam and muscimol which was associated with a greater concentration of benzodiazepine receptors in the striatum and hippocampus compared to RB and FRL rats.

Animals↗
PubMed1987

[Behavior of the turnover of I131-fibrinogen in various diseases of the connective tissue].

It is generally admitted that alteration to the blood coagulation system, particularly the creation of fibrin from fibrinogen may play a pathogenetic role in the complex mechanism that characterises rheumatic diseases of the connective tissue. A study was therefore conducted to see whether accelerated fibrinogen turnover could be demonstrated in such patients. To this end the clearance of fibrinogen marked with I131 was assessed in 25 patients in various stages of connectivitis and 10 controls was measured. The results showed a distinct acceleration in fibrinogen turnover only in patients with highly active rheumatoid arthritis. In contrast patients with rheumatoid arthritis in the regressive phase or with stable progressive systemic sclerosis showed values similar to the control subjects. Finally the possible explanations for this behaviour are examined and the clinical interest of the technique employed is assessed.

Arthritis, Rheumatoid↗
PubMed1986

Procoagulant and fibrinolytic activity of human ovarian carcinoma cells in culture.

We have investigated here the coordinate expression of both procoagulant (PCA) and fibrinolytic (FA) activity of cells from 16 human ovarian carcinoma cases. To avoid interference of contaminating host cells, we used cells isolated in primary culture from ascitic fluid or from solid tumor. The FA was determined in cellular extracts by an amidolytic assay in the presence of fibrin monomers. FA, which was plasminogen dependent in almost all of the cases, showed a wide range of activity (from less than 0.001 to 2.30 UK units/mg protein). The molecular analysis of plasminogen activator (by SDS-PAGE and fibrin autography) showed a single molecular form of 52,000 daltons, inhibited by an antibody against human urokinase. PCA, studied with a one stage clotting assay in disrupted cells, was of tissue thromboplastin type in all instance and varied from 12.0 to 1300 thromboplastin units/10(4) cells. No simple correlation was found between FA and PCA in the cellular samples studied; moreover, for neither parameter was it possible to find any changes with the staging of the disease.

Adult↗
PubMed1986

Mitozolomide activity on human cancer cells in vitro.

The growth inhibitory effects, the reduction of [3H]-TdR incorporation and the perturbation of the cell cycle induced by the new agent mitozolomide on the M14 human melanoma cell line and on the SW626 human ovarian cancer cell line were compared to those produced by BCNU. Flow cytometry showed an interesting difference: at the high concentration mitozolomide induced an accumulation of cells in S middle and S late-G2-M phase of the cell cycle whereas BCNU caused only a block in S late-G2-M. Further studies were aimed at investigating the susceptibility of freshly isolated human ovarian cancer cells to pharmacologically reasonable mitozolomide concentrations. Only in one out of 16 primary cultures of human ovarian cancers was mitozolomide able to induce cell cycle perturbation, suggesting that ovarian carcinoma cells may not be sensitive to this drug.

Aged↗
PubMed1985

[Treatment of chronic cerebrovascular insufficiency and chronic obliterating arteriopathy of the lower extremities with buflomedil hydrochloride].

Research has been carried out into the effects of a new vasoactive substance, buflomedil hydrochloride, on two groups of patients suffering from cerebrovascular insufficiency and obliterating arteriopathy at the lower extremities. Ten clinical parameters were assessed in the first group of patients (insomnia, headache, vertigo, tinnitus, asthenia, shaking, changes in reflexes, anorexia, memory disturbances, problems of concentration and character disturbances); in the second group, the muscular flow of the gastrocnemius as measured by the muscular clearance of NaI131 at rest, during standard exercise conditions, during ten minutes following exercise and in the post-ischaemic phase. The results can be considered satisfactory in both groups, especially after prolonged treatment and in the early stage of the disease. Drug tolerance was very good.

Aged↗
PubMed1985

DNA index of ovarian carcinomas from 56 patients: in vivo in vitro studies.

Out of 130 ovarian cancer patients the DNA index of cells from ovarian carcinoma was studied in 56 cases in which cytospin preparations showed the presence of atypical cells. In 24 patients the population had a diploid DNA index (1.0) and in the others the DNA index ranged from 1.2 to 2.0 (tetraploid). No hypodiploid or hypertetraploid populations were detected. Repeated samples from the same patients did not show any significant differences and primary culture did not alter the DNA index. In contrast, cell cycle phase distribution differed greatly from sample to sample, as also the ratio between DNA diploid and DNA aneuploid populations. Primary culture was successful in 57% of the tumours, with a higher percentage of success in DNA aneuploid tumours. After primary culture the ratio between DNA aneuploid cells and DNA diploid cells increased. In relation to the histological gradings of malignancy, DNA aneuploid cells clustered in the highest grade of malignancy. The mean S-phase for tumours with a DNA index of 1.0 was 3.5 and 14.1% for those with DNA index greater than 1. Ovarian carcinomas show a large difference in DNA index between patients even after primary culture.

DNA, Neoplasm↗
PubMed1983

In vitro and in vivo cytotoxicity of possible uracil metabolites of methylxanthines.

The present study was designed to elucidate the cytotoxic potential of 8 possible substituted uracilic metabolites of methylxanthines. 5-Fluorouracil (5-FU) was used as a reference uracil analogue with cytotoxic activity. Substituted uracil derivatives examined in this study did not affect the proliferative capacity of PHA-stimulated rat lymphocytes, murine L1210 leukaemia and rat chondrocytes. Caffeine had some growth inhibitory activity of extremely high concentrations (greater than 100 micrograms/ml). In vivo administration of 6-amino-5[N-methyl-formylamino]1,3-dimethyluracil (1,3,7-TAU) and 6-amino-5[N-acetylamino]3-methyluracil (7-A3-MAU) caused a transient short-lived reduction of L1210 tumour cell numbers. These observations do not appear to support the hypothesis that substituted uracils are involved in the toxicity of high doses of caffeine in rats.

Animals↗
PubMed1982

[Physiopathological importance of renal ptosis evaluated by renography and photoscintigraphy].

After looking at the possible physiopathological role of renal ptosis in the pathogenesis of arterial hypertension and urinary inflammation, the results of an epidemiological study carried out on about 600 reno-scintigraphic investigations are reported. The study demonstrated the high frequency of the condition in males and its frequent association with monolateral changes in the renographic curve. The second part of the paper assesses the reversibility of renal ptosis and the renographic change in 13 patients in passing from the sitting to Trendelenburg's position. The results show that the change in flow, which may be the cause of the renographic change in the ptosic kidney, is reversible in many patients as it disappears or reduces as the kidney position is corrected. In other patients in whom this does not occur, it can be presumed that the reduction in flow has an organic genesis, namely fibromuscular dysplasia of the renal artery which, as the literature shows, may be looked on as a complication of ptosis.

Fibromuscular Dysplasia↗