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Biomedical subjects

J M Stein

Publications and source records attributed to J M Stein.

At least 37 records · Page 2Linked to original sources
PubMed1989

Activity of cyclosporin A and a non-immunosuppressive cyclosporin against multidrug resistant leukemic cell lines.

Cyclosporin A (CsA) has been shown to increase the sensitivity of multidrug resistant (MDR) cells to chemotherapeutic agents. Although the concentration of drug required to produce this effect is clinically achievable, the use of this drug would be hampered by significant immunosuppression. We report a comparison of the effects of 11-methyl-leucine cyclosporin (11-met-leu CsA), a non-immunosuppressive homolog to the parent drug, on MDR cell lines. Both cyclosporins sensitized resistant cell lines to doxorubicin, including P388 murine leukemia and GM 3639 human T-cell leukemia. The action of the cyclosporins was more pronounced with resistant cells than with sensitive ones. 11-Met-leu CsA was less potent than, but equally effective as, the parent drug. Both agents increased the intracellular accumulation and retention of doxorubicin in MDR cells. The sensitization caused by the cyclosporins was independent of their effects on cyclophilin, calmodulin, and protein kinase C. Furthermore, there were no differences in the binding of labelled CsA to MDR cells compared to the binding to sensitive cells, suggesting that P-glycoprotein was also not the molecular site of action. These studies demonstrate that a non-immunosuppressive cyclosporin can modulate multidrug resistance and suggest its further evaluation for use in clinical trials.

Animals↗
PubMed1988

[Death in utero of a twin during the 2d and 3d trimester of pregnancy].

The study of a series of 9 cases of monofetal death during the last trimester of a twin pregnancy, permits to emphasize the relative frequency of this accident (7.14% in our series, markedly higher than those noted in the literature). An early diagnosis, essentially on ultrasonography, of monofetal death, enables monitoring of the mother and the surviving fetus for whom there is a non negligible risk. It is often necessary to deliver this fetus as soon as it is mature. Systematic and repeated clinical and ultrasonographic monitoring of any twin pregnancy during the third trimester ensures, in a large number of cases, prophylaxis of this accident.

Adult↗
PubMed1987

The effect of sodium periodate treatment on the modulation of the sodium pump in low-potassium type (LK) sheep red cells by the L antigen.

1. The action of sodium periodate and neuraminidase on active and passive K+ transport in low-potassium type (LK) sheep red cells was investigated in relation to the contribution of the Lp and Ll antigens. 2. Active K+ transport in LK sheep red cells was not affected by treatment with sodium periodate (2 mM), or with neuraminidase. 3. Passive K+ transport in LK sheep red cells was increased by sodium periodate treatment in a concentration-dependent manner. The increase was not Cl- dependent, and so differed from the increased passive K+ uptake resulting from N-ethylmaleimide treatment. 4. HK sheep red cells treated with sodium periodate showed small increases in passive K+ uptake, and N-ethylmaleimide treatment used sequentially with sodium periodate resulted in further small increases in passive K+ uptake. 5. In LK sheep red cells the stimulation of active K+ transport by anti-L was impaired by 50% in cells treated with sodium periodate (2 mM) and was slightly lowered in cells treated with neuraminidase. 6. In LK sheep red cells inhibition of passive K+ transport by anti-L was not impaired by sodium periodate treatment (2 mM), or by neuraminidase treatment.

Animals↗
PubMed1987

Inhibition of protein kinase C by antineoplastic agents: implications for drug resistance.

One mechanism by which drugs alter the function of enzymes is through chronic inhibition. To determine whether commonly used cancer chemotherapeutic agents could alter protein kinase C (PKC) and thereby modify the calcium-messenger system, we studied the effect of anthracyclines and vinca alkaloids on the activity of PKC. Doxorubicin, daunomycin, vincristine and vinblastine inhibited the activity of PKC by 50% at concentrations of 150, 120, 350 and 140 microM respectively. Furthermore, we demonstrated the potential for this interaction to occur in intact cells, since doxorubicin blocked the binding of the phorbol ester, PDBu, to its receptor, PKC. The mode of inhibition of PKC was due, at least in part, to interference with the activation of the enzyme by phosphatidylserine. The activity of PKC was increased 15 fold in a highly resistant human breast cancer line, but this increase in enzymic activity was not seen in all lines tested. These studies demonstrate that anthracyclines and vinca alkaloids inhibit PKC, and suggest that chronic antagonism could lead to changes in its activity and function.

Animals↗
PubMed1987

Inhibition of human purine nucleoside phosphorylase by acyclic nucleosides and nucleotides.

In an effort to develop more potent inhibitors of human purine nucleoside phosphorylase (PNP) as immunosuppressive and cancer chemotherapeutic agents, the affinity of the erythrocytic enzyme for 30 acyclic nucleosides, nucleotides and related compounds was determined. Among the acyclonucleosides, 2'-nordeoxyguanosine [2'NDG, 9-(1,3-dihydroxy-2-propoxymethyl)guanine] had a 3-fold greater affinity than acyclovir, and 8-amino-2'NDG was the best inhibitor with Ki = 2.6 X 10(-7) M. The ether moiety of the acyclovir and 2'NDG side-chains was not important for binding. Phosphorylated 2'NDG analogs appeared to act as multisubstrate analogs with optimal binding at low (1 mM) phosphate concentration. The 2'NDG mono- and triphosphates had higher affinities than those reported for the phosphorylated acyclovir derivatives but the diphosphate had a similar Ki value of 9 X 10(-9) M. Poor affinity, independent of phosphate concentration, was found for 9-(2-phosphonoethyl)guanine. The 3'-phosphate derivative of 8-(3-hydroxypropyl)-9-methylguanine inhibited with a Ki = 2 X 10(-5) M in 1 mM phosphate. The chemical syntheses of new analogs are described.

Acyclovir↗
PubMed1987

Central serotonergic influences on renal electrolyte and water excretion.

These studies examined the effects of altered activity or levels of serotonin (5-HT) in the central nervous system (CNS) on renal water and excretion of electrolytes and on arterial blood pressure. Rats were implanted with intracerebroventricular cannulae and then continuously hydrated with a hypotonic solution in order to induce a diuresis. In two separate experimental series, samples of urine were collected before and after intraventricular (i.v.t.) administrations of drug, and the effects on the excretion of sodium were determined. In the first experimental series, 5-HT in the CNS was manipulated by intraventricular administration of p-chloroamphetamine (PCA), an agent known to increase synaptic concentrations of 5-HT. Significant increases in urinary excretion of sodium (UNa V) and the Na/K ratio were observed after the administration of p-chloroamphetamine (200-600 micrograms i.v.t.). p-Chloroamphetamine in large doses also increased blood pressure and antidiuresis. The natriuresis, but not the pressor or antidiuretic responses, were attenuated by pretreatment with either p-chlorophenylalanine, an inhibitor of tryptophan hydroxylase, or fluoxetine, a drug which inhibits the release of 5-HT following the administration of p-chloroamphetamine. Thus, the natriuretic response appeared to be due to a p-chloroamphetamine produced increase of synaptic 5-HT. A further test of the role of 5-HT in the central control of sodium excretion was made in a second experimental series where hydrated rats received intraventricular injections of 5-HT. After direct application of 5-HT to the CNS, significant increases in UNa V and in the Na/K ratio were observed, concomitant with depressor effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

L-antigen and active potassium transport in HK and LK red cells of Barbary sheep (Ammotragus lervia).

1. The potassium concentration in red cells of 21 Barbary sheep showed a bimodal distribution, with five animals of LK type (K+ conc. 30-45 mM) and 16 of HK type (K+ conc. 80-95 mM). 2. Evidence is presented that both Lp and Ll antigens are present on LK Barbary sheep red cells. 3. Active K+ transport in LK Barbary sheep red cells was stimulated 3-5 fold by sheep and goat anti-L. 4. Active K+ transport in HK Barbary sheep red cells was higher than in LK red cells. Five out of six HK animals tested showed no stimulation of active K+ transport with anti-L. One HK animal (2BA2) showed some stimulation of active K+ transport, and also absorbed some anti-L from antisera, suggesting that Lp antigen is present on these red cells. 5. Ouabain-sensitive ATPase in membranes from HK and LK Barbary sheep red cells showed kinetics characteristic of HK and LK membranes of domestic goats and sheep; the ATPase of LK Barbary sheep membranes sensitized with anti-L was stimulated 2-fold due to an alteration in the internal sodium and potassium affinities in favour of sodium.

Adenosine Triphosphatases↗
PubMed1985

Effects of GTP,GDP[beta S] and glucose on adenylate cyclase activity of E. coli B.

Adenylate cyclase activity was measured in suspensions of E.coli B, rendered permeable with toluene. The enzyme was activated in a dose-dependent manner by GTP and by its non-hydrolysable analogue, GTP[gamma S]. In contrast, incubation with GDP[beta S], a non-phosphorylatable analogue of GDP, caused a dose-related inhibition of adenylate cyclase; this was partially overcome by addition of GTP. GTP did not relieve, and GDP[beta S] augmented, the non-competitive and dose-related inhibition of E.coli adenylate cyclase by glucose.

Adenylyl Cyclase Inhibitors↗
PubMed1985

The effect of transcutaneous electrical nerve stimulation on pain after thoracotomy.

The effect of postoperative transcutaneous electrical nerve stimulation (TENS) was evaluated in 24 patients in two randomly selected groups who underwent thoracotomy. The patients in one group received TENS through periincisional electrodes, and the remaining patients were treated with sham stimulator setups. The stimulators remained in place for 48 hours after operation. Subjective pain scores, duration of stay in the recovery room, tolerance to chest physical therapy, complaints of nausea, time to end of mechanical ventilation, and narcotic requirements were evaluated. Patients in the TENS group had significantly lower pain scores during the first 24 hours postoperatively (p = 0.014), shorter recovery room stays (p = 0.013), and better tolerance of chest physical therapy on both day 1 (p = 0.018) and day 2 (p = 0.006). No respiratory complications occurred in either group.

Analgesics, Opioid↗
PubMed1985

Specificity of lactate infusions in social phobia versus panic disorders.

Lactate infusions produced panic attacks in one of 15 patients with social phobia, four of nine with agoraphobia, and 10 of 20 with panic disorder in a blind study. The proportion of patients with social phobia who panicked in response to lactate was significantly lower than that of patients with agoraphobia or panic disorder. These findings lend validity to the DSM-III classification of anxiety states. They also suggest that the pathophysiology of social phobia differs from that of disorders characterized by spontaneous panic attacks.

Adult↗
PubMed1984

The effect of carbacyclin, a prostaglandin analogue, on adenylate cyclase activity in platelet membranes.

The effect of carbacyclin, a chemically stable analogue of prostacyclin, on the activity of adenylate cyclase in platelet membranes was measured, and compared with the effect of PGE1. When GTP was added in concentrations up to 10 microM the activation of adenylate cyclase by carbacyclin was increased, whereas higher concentrations of GTP were inhibitory. The addition of a non-hydrolysable analogue of GDP, guanosine 5'-[beta-thio]diphosphate (GDP[beta S] ) resulted in a dose-dependent inhibition of adenylate cyclase activation by carbacyclin; this inhibition was relieved by adding increased amounts of GTP.

Adenylyl Cyclases↗
PubMed1983

The role of GTP in prostaglandin E1 stimulation of adenylate cyclase in platelet membranes.

Adenylate cyclase activity in platelet membrane preparations was measured in the presence of prostaglandin E1 (PGE1), GTP and a non-hydrolysable analogue of GDP, guanosine 5'-[beta-thio]diphosphate (GDP[beta S]). A dose-dependent inhibition of adenylate cyclase by GDP[beta S] was observed that could be reversed either by adding increased amounts of GTP or of PGE1.

Adenylyl Cyclase Inhibitors↗