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Biomedical subjects

S Goldenberg

Publications and source records attributed to S Goldenberg.

At least 37 records · Page 2Linked to original sources
PubMed1996

MDR1/P-glycoprotein function. I. Effect of hypotonicity and inhibitors on rhodamine 123 exclusion.

The MDR1 protein (P-glycoprotein) is a membrane ATPase whose expression results in resistance to several anti-tumor drugs. It has been proposed that the MDR1 protein, in addition to its pumplike properties, can function as (Gill et al. Cell 71: 23-32, 1992; Altenberg et al. Cancer Res. 54:618-622, 1994) or mediate the activity of (Hardy et al. EMBO J. 14: 68-75, 1995) a hypotonic stress-induced Cl- current. In addition, one study found that drug transport and Cl- channel-associated functions of MRD1 were separable and mutually exclusive and that, when cells were swelled, the MDR1 protein could not transport substrate. This hypothesis was tested in four pairs of isogenic cell lines with MDR1 transfectants expression 8,000-55,000 MDR1 antibody binding sites per cell. Cytoplasmic exclusion of rhodamine 123 was used as an indicator of MDR1 function to measure the effect of hypotonic stress, MDR1 inhibitors, and Cl- channel blockers on MRD1 transport function. It was found that MDR1 activity and its inhibition by cyclosporine A or flufenamic acid were unaffected by hypotonicity alone or in combination with Cl- channel blockers.

3T3 Cells↗
PubMed1996

Structural requirements for activity of propafenone-type modulators in P-glycoprotein-mediated multidrug resistance.

The sodium channel blocker propafenone and a series of analogs have been identified as effective modulators of P-glyco-protein-mediated multidrug resistance in human tumor cells. A series of closely related structural homologues showed a highly significant correlation between lipophilicity and pharmacological effect. Reduction of the carbonyl group as well as conversion to a methylether led to a remarkable decrease in activity, whereby lipophilicity lost its predictive character as the main determinant for modulator potency. Similarly, the relative positioning of the acyl- and propanolamine side chains also influences activity, so the distance between carbonyl group and nitrogen atom seems important.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Hypergastrinemia following gastrocystoplasty in rats.

Gastrocystoplasty has been previously described as an effective method of bladder augmentation or replacement. Twenty-four female Wistar rats were divided into three groups of eight animals each: control (G1), partial gastrectomy with the gastric body (G2) and gastrocystoplasty with the gastric body (G3). The period of observation was 2 months and the parameter assessed was serum gastrin. Increases in serum gastrin were seen in 62.5% (5/8) of rats in group 2 and in 50% (4/8) of rats in group 3. Our results suggest that, in rats, hypergastrinemia is induced by the partial surgical removal of the gastric body and is not due to gastrocystoplasty.

Animals↗
PubMed1994

Characteristics of P388/VMDRC.04, a simple, sensitive model for studying P-glycoprotein antagonists.

Cross-resistance to chemotherapeutic drugs is a significant problem in the treatment of patients with cancer. The discovery that this phenomenon is associated with the overexpression of a membrane glycoprotein, P-glycoprotein, which acts as a drug efflux pump, has provided a new target for drug development. To develop a model for identifying new compounds which can block the function of P-glycoprotein, we infected P388 mouse leukemic cells with a retrovirus containing a cloned human MDR1 complementary DNA. The new cell line, P388/VMDRC.04, incorporated and overexpressed the human gene as evidenced by Southern blots, increased mRNA and protein synthesis, and recognition by the MRK16 monoclonal antibody. P388/VMDRC.04 was cross-resistant to colchicine, vincristine, and doxorubicin, and the degree of resistance correlated with a reduction in cellular drug accumulation. Unlike many cell lines selected for resistance by growth in increasing concentrations of drug for prolonged periods of time, these cells did not show alternative mechanisms of resistance such as increased synthesis of glutathione or alterations in topoisomerase II. In addition, the sensitivity of P388/VMDRC.04 cells was completely restored by cyclosporin A and trans-flupenthixol. P388/VMDRC.04 cells were subcloned and 10 clones were picked for in vivo evaluation. One subclone grew similarly to parental cells in female BALB/c x DBA/2 F1 mice and showed no responsiveness to therapeutic doses of vincristine or etoposide. The combination of vincristine with cyclosporin A significantly increased the survival of mice inoculated with P388/VMDRC.04 cells. The availability of a cell line that displays the MDR phenotype, overexpresses human P-glycoprotein, but does not contain alterations in at least two well-defined alternative mechanisms of resistance, and that can be grown in simple animal models should facilitate the development of new agents active against this form of chemotherapeutic drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Favourable results of treatment of narrowed saphenous vein grafts with Palmaz-Schatz stent implantation.

Although conventional balloon angioplasty of saphenous vein grafts can be performed with an acceptable acute success and complication rate, restenosis remains a major problem. However, this may be overcome by the implantation of Palmaz-Schatz stents. Palmaz-Schatz stent deployment was performed in our institution in 43 patients who were referred for PTCA of stenosed saphenous vein grafts. Thirty-seven were located at the mid-portion of the graft, seven at the ostium and six at the distal anastomosis. Overall, we used 59 standard length (15 mm) Palmaz-Schatz stents and 22 short (7 mm) stents. In 15 lesions (30%) multiple stents were implanted in tandem to treat diffuse disease. Angiographic success was achieved in 47 of the 50 attempted lesions (94%). Major cardiac complications occurred in three patients. Two patients had procedures complicated by the development of a Q wave myocardial infarction, one of whom underwent urgent CABG. One patient died. There was no episode of subacute thrombosis. The angiographic follow-up of 37 lesions (80% of eligible lesions) at a mean time of 5 +/- 2 months (range 1-8) showed a restenosis rate of 11% and residual post-stent diameter stenosis was associated with a significantly higher restenosis rate. However, no restenosis occurred in lesions receiving multiple stents. Clinical follow-up was performed in all patients, and at a mean of 25 months after the procedure, 64% were free from clinical events, including recurrent angina. Palmaz-Schatz stent implantation is an effective and safe procedure to treat narrowed vein grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Characterization of proteinases in trypanosomatids.

Proteinases are important factors in the pathogenicity of many parasitic diseases. In this study, the proteolytic activities of 10 trypanosomatids from five different genera (Crithidia, Phytomonas, Endotrypanum, Trypanosoma and Leishmania) were determined by SDS-PAGE containing copolymerized gelatin as substrate. In almost all species we could detect two proteolytic classes, cysteine- and metalloproteinases, based on the inhibition of their activities by E-64 and 1,10-phenanthroline, respectively. In all cases, the metalloproteinase activities did not change over a broad pH range (from 5.5 to 10). E. schaudinni, T. mega, T. dionisii, C. luciliae, C. fasciculata, C. oncopelti and C. guilhermei expressed one or two metalloproteinases of 45-66 kDa, whereas in P. serpens and P. hyssopifolia a double band of this endopeptidase was detected at 94 kDa. In contrast, no metalloproteinase activity was observed in L. tarentolae. The optimal pH for the cysteine-proteinase activities was acidic (about 5.5). In E. schaudinni, T. mega and in Crithidia sp., these proteinases had an apparent molecular weight of 66-94 kDa, while L. tarentolae expressed a broad band from 29 to 45 kDa. In Phytomonas sp., this class of endopeptidase showed a unique feature, in that major cysteine-proteinases were found at 29-66 kDa, but multiple, low-activity bands were detected from 116 to 200 kDa. The most striking characteristic, however, was the very intense cysteine-proteinase activity expressed by T. dionisii (29-66 kDa). We conclude that these differences in the proteolytic profiles could be useful markers to characterize and compare trypanosomatids.

Animals↗