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P Calabresi

Publications and source records attributed to P Calabresi.

At least 217 records · Page 12Linked to original sources
PubMed1987

Artificial capillary culture studies of human tumor cell growth, differentiation, and marker production.

The morphological characteristics and the production of biochemical markers were determined for 8 human tumor cell lines grown in artificial capillary culture. Comparisons were made with nude mouse xenografts and conventional monolayer or suspension cultures. Capillary histologies reproduced the features of neoplastic differentiation and glandular formation exhibited by the original human tumors and xenografts. The concentrations of specific biochemical markers, such as carcinoembryonic antigen, aspartate aminotransferase, and immunoglobulin, were higher in the pericellular culture medium in capillary culture. The capillary environment influenced the expression of biochemical heterogeneity by the DLD-1 colon carcinoma cell line and its derivative clones. Spontaneous differentiation of K562 leukemia cells was increased in the capillary system. These results indicate that the artificial capillary is a useful and relevant system for the study of cultured human tumor cells.

Animals↗
PubMed1986

Responsiveness to 'autoreceptor' doses of apomorphine inversely correlated with the firing rate of dopaminergic A9 neurons: action of baclofen.

Supersensitivity of dopamine (DA) autoreceptors develops soon after acute treatments with baclofen or gamma-butyrolactone, two drugs which suppress DA neuronal firing. We have hypothesized that this effect might reflect a condition associated with the low firing rate of DA cells induced by such treatments rather than a long-term adaptive modification of DA receptor sensitivity. In this study we show that the degree of the intravenous apomorphine-induced inhibition of A9-DA neurons is inversely correlated to the basal firing rate of these neurons. When administered after baclofen, apomorphine further reduced DA cell activities in a manner proportional to the predrug firing rate, as in control rats. Since the minute doses of apomorphine which were used are thought to selectively activate DA autoreceptors, our finding may indicate that DA autoreceptor stimulation is more effective when the activity of the DA neurons is low, or it is decreased by drugs such as baclofen.

Animals↗
PubMed1986

Muscarinic modulation of calcium dependent plateau potentials in rat neostriatal neurons.

Intracellular recording from neostriatal neurons in rat brain slices revealed effects of the acetylcholine (ACh) agonist carbachol (Cch, 1-10 mumol/l), of the anticholinesterase physostigmine (10 mumol/l) and of the muscarinic antagonist atropine (10 mumol/l) on plateau potentials elicited in the presence of K-blockers. Plateau potentials elicited in the presence of K-blockers were Ca-dependent, since they persisted in Na-free solution, were resistant to tetrodotoxin (TTX, 3 mumol/l) and blocked by Cd (0.1-0.5 mmol/l). Cch reduced the duration of the plateau potentials and made them more susceptible to fatigue. These effects were antagonized by atropine (1-10 mumol/l), but not by Ba (100-200 mumol/l) or 4-aminopyridine (4-AP, 0.5 mmol/l). Physostigmine (10 mumol/l) had the same atropine-sensitive effects as Cch on the plateau potential. Atropine (10 mumol/l), by itself, prolonged the duration of the plateau potential. High concentrations (100 mumol/l) of Cch did not further reduce the duration of the plateau potential, instead, the duration re-increased with prolonged exposure. The re-increase of the plateau-spike duration was later masked by bursting activity. The opposing effects of low and high concentrations of Cch on the plateau potential duration corresponded to effects of this drug on intrastriatally evoked EPSPs in that low concentrations of Cch reduced the EPSP amplitude, but high concentrations re-increased it after a transient decrease. It is concluded that the muscarinic effect of ACh in the neostriatum is to modulate Ca-influx and that this effect is exerted in a tonic manner.

Acetylcholine↗
PubMed1986

Action of morphine on rat cortical neurons intracellularly recorded in vivo: evidence for an excitatory postsynaptic effect which is naloxone insensitive.

The action of morphine, applied either iontophoretically (40-200 nA balanced current) or systemically (5-10 mg/kg, intraperitoneally) to rat cortical neurons, was investigated in vivo, using intracellular electrodes. Morphine increased the apparent input resistance and increased the number of both spontaneous and evoked action potentials. Several cells, which normally generated single spikes, generated bursting potentials; neurons with bursting activity increased their activity. Naloxone, iontophoretically or systemically applied, did not reverse or prevent the morphine-induced excitation. The iontophoretic administration of cadmium suggested that the effects of morphine were due, at least in part, to a postsynaptic site of action. It is suggested that the increase of cellular excitability induced by morphine could contribute to its production of seizures in cortex.

Action Potentials↗
PubMed1986

Medical oncology manpower training: a position statement of the American Society of Clinical Oncology.

The evolution of Medical Oncology is facing its first major crisis, that of oversupply of trained oncologists. The tabulated number of certified medical oncologists does not constitute all of the physicians practicing Medical Oncology in the United States. Because of the adequate supply of medical oncologists in clinical practice, but a deficiency of academic oncologists dedicated to research careers, a reduction in training programs should emphasize those programs that lack research opportunities. These recommendations are in keeping with the report of the Long-Range Planning Committee of the American Society of Clinical Oncology of March 21, 1984. Plans to expedite these goals are being established.

Medical Oncology↗
PubMed1986

Induction of doxorubicin resistance in heterogeneous human colon tumor cells by N-methylformamide.

Two clonal subpopulations of cells (termed A and D) obtained originally from a heterogeneous human colon adenocarcinoma were studied in vitro with regard to possible modification of responsivity to graded doses of doxorubicin (ADM) after long-term growth in medium containing the differentiating agent N-methylformamide (NMF). Non-NMF-adapted clone A and D cells exhibited biphasic response curves after exposure to graded doses of ADM (0-1.4 micrograms/ml, 1 hour, 37 degrees C). The inactivation slopes for the initial regions of the survival curves were 0.13 and 0.39 g/ml for clone A and D cells, respectively. NMF-adapted cells, however, exhibited decreased sensitivity to ADM killing as the inactivation slopes for the initial region of the survival curves increased to 0.26 and 0.59 g/ml for clone A and D cells, respectively. The final slopes of the biphasic response curves (doses above about 0.8 micrograms/ml) were not significantly different between clone A and clone D tumor cells in either the non-NMF- or NMF-treated conditions. These data on ADM responses after differentiation induction by NMF indicate that the combination of differentiation-inducing agents with certain chemotherapeutic agents may produce therapeutically undesirable effects and that preclinical data are necessary prior to implementation of possible combined-modality protocols.

Adenocarcinoma↗
PubMed1985

Dopamine decreases cell excitability in rat striatal neurons by pre- and postsynaptic mechanisms.

The mechanism by which dopamine (DA) decreases the amplitude of the EPSP-IPSP sequences evoked by cortical stimulation was investigated by means of electrophysiological and biochemical methods. Intracellular recordings indicate that DA decreases the amplitude of the excitatory and inhibitory events by reducing the increase in membrane conductance measured at the peaks of the EPSP-IPSP. The non-synaptic input resistance was not modified. In addition the catecholamine (+50/+200 nA balanced current) was shown to decrease the action of glutamate (-30/-80 nA balanced current) and GABA (+40/+100 nA balanced current) when iontophoretically applied. These observations suggest that DA interferes with the excitatory (glutamatergic) and inhibitory (GABAergic) transmission at the postsynaptic site in striatal neurons. However, the depression of cellular excitability elicited by DA could not be ascribed only to its interaction with synaptic transmission at the postsynaptic level. In fact the catecholamine also inhibited spike frequency driven by depolarizing pulses and decreased the depolarization-induced release of glutamate at the presynaptic site, as shown by biochemical experiments with striatal synaptosomal preparations. A neuromodulatory role of DA in the depression of the excitability of striatal neurons by presynaptic and postsynaptic mechanisms is suggested.

Animals↗
PubMed1985

Electrical stimulation of mesencephalic cell groups (A9-A10) produces monosynaptic excitatory potentials in rat frontal cortex.

Electrical stimulation of the ventral tegmental area and substantia nigra produces monosynaptic and polysynaptic excitatory postsynaptic potentials in rat frontal neurons that can be recorded intracellularly. The electrophysiological characteristics of the monosynaptic responses and the possibility that dopamine (DA) mediates these events are discussed.

Animals↗
PubMed1985

Rationally designed combination chemotherapy for the treatment of patients with recalcitrant psoriasis.

In an effort to improve clinical response and reduce systemic toxicity, nine patients with recalcitrant psoriasis were treated with rational combinations of chemotherapeutic agents. Five patients received methotrexate by injection, 7.5 or 10 mg, followed 1 hour later by intravenous 5-fluorouracil, 170 to 562 mg/m2, on a weekly schedule. Four patients received oral triacetyl-azauridine, 2 to 4 gm daily, in combination with intravenous 5-fluorouracil, 225 to 600 mg/m2, administered every week. Three patients experienced greater than 75% clearing of disease, five patients experienced greater than 50% clearing, and only one patient failed to respond. Response rates did not differ between the two treatment groups. Adverse effects of these therapies were mild and infrequent. We conclude that 5-fluorouracil in combination with either methotrexate or triacetyl-azauridine is a relatively safe and effective alternative for the therapy of patients with severe psoriasis.

Adult↗
PubMed1985

Differential characteristics of two newly established human breast carcinoma cell lines.

Two human breast carcinoma cell lines, EP and MW, were established in culture from malignant pleural effusions. In addition to producing tumors in antithymocyte serum-immunosuppressed mice, both cell lines showed epithelial characteristics and anchorage-independent growth in soft agar. EP and MW differed in morphology (spindle-shaped versus round), chromosomal mode (hyperdiploid versus near triploid), estrogen receptor content (43.8 versus 5.1 fmol/mg protein), cloning efficiency (0.24 versus 15%), and activities (milliunits/10(6) cells) of creatine phosphokinase (25.7 versus 62.6) and lactate dehydrogenase (346.7 versus 778.5). Electron microscopy revealed that MW cells had more perinuclear filamentous material and more frequent intracytoplasmic vacuole formation than did EP cells. While having no effect on MW cells at the concentrations studied (10(-5) to 10(-11) M), beta-estradiol (10(-7) M) stimulated the growth of EP cells by 106% over the hormone-depleted control. In a variety of systems, EP was consistently the more drug sensitive of the two lines. In vitro, EP was significantly (p less than 0.001) more sensitive to methotrexate, vincristine, and 5-fluorouracil, respectively. In antithymocyte serum-mouse xenografts, EP displayed a greater response to three different dosages of a combination of cyclophosphamide, methotrexate, and 5-fluorouracil. One such dosage (cyclophosphamide, 32.0 mg/kg/day; methotrexate, 13.0 mg/kg/day; 5-fluorouracil, 190.0 mg/kg/day; for 1 day) reduced EP and MW tumor weights to 5.9 and 41% of controls, respectively. These results correlated well with the clinical responses.

Aged↗
PubMed1984

Dopaminergic and noradrenergic responses in the hippocampal slice preparation. Evidence for different receptors.

The effects of iontophoretic applications of dopamine (DA) and noradrenaline (NA) on potentials evoked by the stimulation of the hippocampal slice preparations were investigated. Dopamine, ejected at the soma, produced an increase of the amplitude of the population spike of CA1 pyramidal cells; NA had an excitatory action on some responses, inhibitory on others. The field-excitatory postsynaptic potentials (EPSPs) were unaffected by ejection of DA and NA on the dendritic tree. Domperidone, a dopaminergic antagonist, blocked the increase of the population spike induced by DA, but was unable to antagonize noradrenergic responses. Timolol, a beta-adrenergic antagonist, blocked the excitatory action of NA, but did not modify either the effect of DA or the inhibition induced by NA. Phentolamine, an alpha-antagonist, antagonized only the inhibition induced by NA. These results indicate that DA and NA modulate the activity of hippocampal neurones by interacting on different receptors.

Animals↗
PubMed1984

Dopamine modulates CA1 hippocampal neurons by elevating the threshold for spike generation: an in vitro study.

Intracellular recordings were obtained from CA1 neurons of rat hippocampal slices preparation. Dopamine applied by perfusion (10(-5)-10(-7) M), microdrop (10(-4) M) and iontophoresis (+80, +200 nA balanced current) inhibited "spontaneous" and evoked action potentials. An increase in current injection restored the evoked action potentials which appeared unmodified. Membrane potential was not modified in 60% of the neurons; in the remaining ones, a slow depolarization was observed. Membrane resistance, measured at rest, was not modified by dopamine. Calcium-mediated events such as bursting activity and afterhyperpolarization, mainly in the late component, were also attenuated by the catecholamine. These effects were antagonized by domperidone, a dopaminergic antagonist. Calcium spikes, evoked in tetrodotoxin- and tetraethylammonium-poisoned slices, were reversibly inhibited by dopamine. Since an increase in the amplitude of a depolarizing pulse of injected current was able to evoke both sodium and calcium action potentials suppressed by dopamine without change in shape or duration, it is concluded that this catecholamine depresses cellular excitability by altering the interaction between membrane voltage and sodium and calcium entry and the subsequent increase in potassium conductance.

Animals↗
PubMed1984

Potentiation of 5-fluoro-2'-deoxyuridine antineoplastic activity by the uridine phosphorylase inhibitors benzylacyclouridine and benzyloxybenzylacyclouridine.

At a nontoxic dose (50 microM), the two potent uridine phosphorylase inhibitors, benzylacyclouridine and benzyloxybenzylacyclouridine (BBAU), potentiated 5-fluoro-2'-deoxyuridine (FdUrd) growth inhibition of human pancreatic carcinoma (DAN) and, to a lesser extent, human lung carcinoma (LX-1) cells in culture. BBAU was more effective than benzylacyclouridine. BBAU (50 microM) enhanced the cytocidal effect of FdUrd (1 microM, 3 hr) on DAN grown on soft agar from 75 to 88%. In antithymocyte serum-immunosuppressed mice bearing DAN, the mean tumor weight in animals treated with FdUrd (50 mg/kg/day for 2 days) was 11% less than that of untreated controls. When BBAU (10 mg/kg/day for 2 days) was coadministered, the mean tumor weight at Day 10 was 78% less than untreated controls, with no apparent host toxicity, clearly demonstrating the potentiation of the antitumor effects of FdUrd by BBAU. The fact that DAN responded better than LX-1 to benzylacyclouridine and BBAU could be due, in part, to the lower relative activity of thymidine phosphorylase to uridine phosphorylase in DAN compared to LX-1. The activities of other enzymes involved in FdUrd metabolism, thymidine kinase, uridine kinase, orotate phosphoribosyltransferase, 5'-nucleotidase, and dihydrouracil dehydrogenase, did not differ between the two cell lines.

Animals↗