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Biomedical subjects

D Lotan

Publications and source records attributed to D Lotan.

At least 73 records · Page 4Linked to original sources
PubMed1987

Modulation of polycation-induced redistribution of melanoma cell surface anionic macromolecules by retinoic acid.

The ability of cationized ferritin (CF) to redistribute negatively charged cell surface molecules has been shown to increase after malignant transformation. Pretreatment of murine melanoma S91-C2 and B16-F1 cells with retinoic acid (RA), which suppresses their transformed phenotype, decreased the ability of CF to cluster surface anionic sites. In contrast, a similar pretreatment of RA-resistant mutant clone S91-C154 and subline B16-F10 caused only a minor reduction in CF-induced patching of anionic sites. These results indicate that the effect of RA on the redistribution of negatively charged cell surface molecules is related to the growth-inhibitory action of this vitamin A metabolite.

Animals↗
PubMed1987

Colchicine reduces proteinuria in passive Heymann nephritis.

Colchicine was given to rats in the heterologous phase of passive Heymann nephritis to see whether this drug could reduce proteinuria. Treatment with 0.06 mg/day for 14 days caused significant reductions in proteinuria and albuminuria. Administration of dimethyl sulfoxide (DMSO) alone or in combination with colchicine also reduced protein and albumin excretion. In a long-term experiment, rats treated with colchicine had significantly less proteinuria. After stopping therapy, urine protein excretion was similar to controls. No differences in glomerular C3 and IgG deposition were found between treated and control rats 24 h, 3,7 and 14 days after immunization. Depressed serum C3 levels were measured at 24 h in colchicine-treated rats. No difference in serum-circulating immune complexes was detected between the two groups. Concurrent administration of indomethacin and colchicine to rats with passive Heymann nephritis (PHN) partially reversed the reduction in proteinuria and albuminuria seen in rats treated with colchicine alone. The G.F.R, however, was significantly reduced in colchicine-treated rats as well as in rats treated with colchicine and indomethacin. Serum cholesterol and triglyceride levels were significantly lower in colchicine-treated rats than in controls. Serum cholesterol concentrations in rats given both colchicine and indomethacin were similar to control values. These findings suggest that colchicine reduces urine protein and albumin excretion, and hyperlipidemia in PHN. The finding that indomethacin partially blocks the effects of colchicine suggests that renal prostaglandin stimulation by colchicine may have been involved in the reduction in proteinuria.

Animals↗
PubMed1986

Interactions of dimethyl sulfoxide and nonsteroidal anti-inflammatory agents in passive Heymann's nephritis.

The effect of treatment with indomethacin on the ability of dimethyl sulfoxide (DMSO) to reduce proteinuria in rats with passive Heymann's nephritis (PHN) was studied. PHN rats treated with DMSO alone excreted significantly less protein by day 14 than PHN rats treated with buffer or with indomethacin alone. Rats treated with DMSO excreted 19 +/- 6.0 mg protein/24 hr, and those treated with DMSO and indomethacin excreted 161 +/- 27.4 mg protein/24 hr (P less than 0.001). Rats treated with DMSO alone had significantly higher serum albumin and significantly lower serum cholesterol and triglyceride concentrations than those given the two drugs together. Glomerular deposits of C3 were reduced in DMSO-treated rats, but serum C3 concentrations and rat antirabbit serum antibody titers were similar in the two groups. When a higher dose of indomethacin (5 mg/kg) plus DMSO was used, protein excretion was significantly reduced. Rats treated with DMSO and acetylsalicylic acid (ASA) (37 mg/kg/day) or DMSO and meclofenamate (5 mg/kg/day) did not have a significant reduction in protein excretion compared with untreated controls. High-dosage indomethacin alone did not reduce proteinuria. Low doses of nonsteroidal anti-inflammatory agents therefore appear to block the effect of DMSO on proteinuria. This was in marked contrast to the finding of reduction of proteinuria induced by larger doses of indomethacin (5 mg/kg) plus DMSO. DMSO did not reduce proteinuria in rats with nephrosis induced by puromycin of aminonucleoside.

Animals↗
PubMed1985

Inhibition of tumor cell colony formation in culture by a monoclonal antibody to endogenous lectins.

The presence of endogenous, galactoside-specific lectin molecules on the surface of various neoplastic cells has been demonstrated recently using monoclonal antibody (mAb) 5D7 [Raz et al., EMBO (Eur. Mol. Biol. Organ.) J., 3: 2979, 1984]. The effect of this mAb on the growth of several transformed and tumor cell lines of murine and human origin was investigated using in vitro techniques. A dose-dependent reduction (30 to 100%) in colony formation on a solid substrate or in a semisolid medium was observed when the cells were cultured in the presence of 15 to 100 micrograms of mAb 5D7 per ml of medium. Inhibition of anchorage-independent growth was more pronounced (2- to 3-fold) than inhibition of anchorage-dependent growth for most of the cells. The growth-inhibitory effects of mAb 5D7 were not the result of a cytolytic activity, for neither DNA nor protein synthesis was suppressed in semiconfluent cell cultures after 3 days of exposure to the antibody. Other mAbs that recognize cell surface components, such as chondroitin sulfate or fibronectin, failed to inhibit colony formation. These results suggest that endogenous tumor cell-surface lectin molecules may be involved in intercellular interactions or interactions between the cells and exogenous ligands; these interactions are important for growth regulation.

Animals↗
PubMed1984

Monoclonal antibodies to endogenous galactose-specific tumor cell lectins.

A monoclonal antibody, 5D7, was obtained after immunization of syngeneic mice with B16 melanoma cell extracts enriched for endogenous lectin activity and screening for inhibition of lectin-mediated hemagglutination. Binding of this antibody to affinity-purified B16 melanoma galactoside-specific lectin was revealed by solid-phase radioimmunoassay and binding to the surface of viable B16 cells was demonstrated by indirect immunofluorescence. Inhibition of lectin activity and cell surface labeling by 5D7 antibody were also found with several types of cultured human and murine cells including melanoma, sarcoma and carcinoma. This monoclonal antibody should be useful for evaluating the role of tumor cell surface lectins in intercellular interactions and metastasis.

Animals↗
PubMed1984

Retinoic acid restores shape-dependent growth control in neoplastic cells cultured on poly(2-hydroxyethyl methacrylate)-coated substrate.

The ability of retinoic acid to modulate cell-shape-dependent growth of untransformed (human skin fibroblasts and mouse embryo Swiss 3T3 fibroblasts) and neoplastic cells (human cervical carcinoma HeLa-S3, osteosarcoma Hs791, and murine melanomas B16-F1, S91-C2 and S91-C154) was examined. The cells were plated on tissue culture dishes coated with increasing concentrations of poly(2-hydroxyethyl methacrylate), poly(HEMA) which cause a gradual decrease in substrate adhesiveness. Untreated cells as well as cells pretreated with 10 microM retinoic acid for 4 days displayed a similar graded series of cell shapes between flat and spherical on these modified substrata, with the exception of HeLa-S3 cells which were rounded and loosely attached even on uncoated plastic dishes. A marked cell-shape-dependent decrease in DNA synthesis was observed in untransformed human skin fibroblasts, Swiss 3T3 fibroblasts and neoplastic human Hs791 cells 20 h following plating of untreated cells on poly(HEMA)-coated substrates of decreasing adhesiveness. Conversely, in B16-F1, HeLa-S3 and S91-C154 cells DNA synthesis was only slightly affected by changes in cell shape. Pretreatment with retinoic acid rendered DNA synthesis in Swiss 3T3, Hs791, B16-F1 and S91-C2 cells much more sensitive to changes in cell shape. In contrast, retinoic acid exerted only marginal effects on the sensitivity of DNA synthesis to changes in cell shape in untransformed human skin fibroblasts, in HeLa-S3 cells and in the retinoic-acid-resistant S91-C154 cells. The results suggest that retinoic acid can restore in certain tumor cells the tight coupling between cell shape and DNA synthesis that exists in untransformed cells.

Cell Communication↗
PubMed1984

Enhancement by retinoic acid of the sensitivity of different tumor cell lines to the sialic acid-specific toxin of Entamoeba histolytica.

Treatment of several tumor cell lines, including the murine melanomas B16 and S91 and the human sarcoma Hs791 and Hs705, with retinoic acid resulted in an increased sialylation of specific cell surface membrane sialoglycoproteins. This treatment also augmented the sensitivity of these cells to the cytopathic effects of a sialic acid-specific toxin from Entamoeba histolytica. In contrast, a similar treatment with retinoic acid of a retinoic acid-resistant mutant clone S91-C154, which does not increase sialylation of cell surface glycoproteins, failed to alter the susceptibility of the cells to the E. histolytica toxin. These results imply that cell surface sialoglycoproteins serve as receptors for the amoebic toxin.

Animals↗
PubMed1984

Reduction of protein excretion by dimethyl sulfoxide in rats with passive Heymann nephritis.

Passive Heymann nephritis, a model of immune complex nephritis, was produced in rats by injection of rabbit antibrush border membrane vesicle antibodies to examine the effect of treatment of epimembranous glomerulonephritis with dimethyl sulfoxide. Administration of DMSO twice a day, 5 days a week for 4 weeks significantly reduced protein excretion in the autologous phase of the model. This beneficial effect occurred in animals in which treatment was started a day after administration of the antibody and persisted for 4 weeks after treatment was discontinued. Serum triglyceride concentrations were significantly decreased, whereas, BUN, serum cholesterol, and globulin levels were significantly, but not reproducibly, reduced. That DMSO did not reduce proteinuria to normal values in rats treated after proteinuria was well established, but was able to reduce proteinuria significantly. Treatment of normal rats and those with nephrotoxic serum nephritis did not reduce protein excretion. Glomeruli of rats with passive Heymann nephritis treated with DMSO studied by immunofluorescent microscopy appeared to have less fluorescence for IgG than control rats, but these differences were not significant. However, C3 deposits were significantly decreased in treated rats, but only during the first week of the disease and in vitro C3 fixation was also significantly reduced in glomeruli of rats that had been treated with DMSO. There was very little effect on serum complement activity: CH50 was reduced only on day 1 of treatment, whereas the alternate pathway activity and serum C3 concentration were unaffected. DMSO may therefore reduce protein excretion, in part, by inhibiting C3-dependent proteinuria. These studies indicate that DMSO is capable of significantly reducing protein excretion in rats with passive Heymann nephritis and that its action may involve reduction of complement deposition within the glomeruli during the heterologous phase. Toxic effects included a 2.5% mortality and decreased weight gain while being treated with larger doses of DMSO. Treatment with a much smaller dose succeeded in reducing proteinuria significantly without affecting weight gain. There was no evidence of drug-induced liver or renal damage.

Animals↗
PubMed1984

Correlation of retinoic acid-enhanced sialyltransferase activity and glycosylation of specific cell surface sialoglycoproteins with growth inhibition in a murine melanoma cell system.

Retinoic acid inhibits the proliferation of the murine melanoma clone S91-C-2 cells, enhances the glycosylation of specific cell surface sialoglycoproteins, and stimulates sialytransferase activity. Mutant clones, selected from the S91-C-2 cells for resistance to the growth-inhibitory effect of retinoic acid, were used to explore whether cell surface modulation by retinoic acid is related to growth inhibition. Glycoprotein synthesis was assessed by analysis of [3H]glucosamine incorporation into glycoconjugates, and cell surface sialo- and galactoglycoproteins were analyzed after radiolabeling by the NaIO4:NaB3H4 and the neuraminidase plus galactose oxidase:NaB3H4 methods, respectively. The cells were solubilized and the labeled molecules were separated by polyacrylamide gel electrophoresis and identified by fluorography. Sialytransferase activity was measured in detergent-solubilized cells, using cytidine 5' -monophosphate-[14C]sialic acid as a sugar donor and asialofetuin as an exogenous acceptor. The results demonstrated that retinoic acid enhanced [3H]glucosamine incorporation into a Mr 160,000 glycoprotein in the S91-C-2 cells but not in any of the resistant mutant clones, while the pattern of [35S]methionine-labeled proteins was not modified in either the sensitive or the resistant clones. Radiolabeling of a Mr 160,000 sialoglycoprotein on the surface of S91-C-2 and of several retinoic acid-sensitive subclones of S91-C-2 was augmented by retinoic acid. A considerably smaller effect was observed on the labeling of Mr 160,000 sialoglycoprotein on one of the resistant clones, and no significant effect could be detected on the other resistant mutant clones. Sialytransferase activity was increased 2- to 3-fold by retinoic acid in the S91-C-2 cells and in several sensitive subclones, but not in any of the resistant mutant clones. Tetradecanoylphorbol acetate, which inhibits the proliferation of both retinoic acid-sensitive and retinoic acid-resistant cells, failed to increase either sialyltransferase activity or cell surface labeling of sialoglycoproteins. These findings suggest that the ability of retinoic acid to stimulate sialyltransferase activity and glycosylation of cell surface glycoproteins is related to the growth-inhibitory effect of this compound.

Animals↗
PubMed1983

Idiopathic hypercalciuria: a familial generalized renal hyperexcretory state.

Twenty-two children with idiopathic hypercalciuria (IH) as well as their parents and siblings were compared to 29 control children and their parents and siblings. Urinary calcium excretion following calcium deprivation or calcium loading was significantly higher in parents and siblings of the IH children than in the corresponding controls. Significantly higher rates of glomerular filtration and increased urinary excretion of sodium potassium and phosphate were found in all family members in the IH group as compared to controls. Significant positive correlations of the five variables studied (glomerular filtration and urinary excretion of calcium, phosphate, sodium, and potassium) were noted within individuals and also within families, both in the IH and the control groups, notwithstanding the lower mean levels in the latter. Serum concentrations of calcium, phosphate, potassium, and sodium were similar in the IH and controls. The distributions of all urinary variables in both the IH and control groups were unimodal with considerable overlap of the two groups, suggesting that IH may be a single entity, possibly representing the upper end of normality. Our data seem to indicate that IH is more likely to be due to nutritional than to genetic factors, since maintenance of sodium potassium homeostatis in the face of increased excretion necessitates increased ingestion of these electrolytes, while increased sodium ingestion is known to be associated with increased urinary excretion of calcium, potassium, and phosphate.

Adult↗
PubMed1983

Renal function in patients with cystic fibrosis.

Renal handling of sodium, potassium, calcium and phosphorus was investigated in 9 patients with cystic fibrosis (CF). Both under baseline conditions and during saline-induced diuresis, urinary excretion rate of sodium (UNaV), potassium, phosphorus and calcium did not differ significantly from control values although the fractional excretion of sodium was significantly higher in patients with CF during saline diuresis. When distally acting diuretics were administered, this difference between CF patients and controls was magnified and in addition, UNaV in CF patients was also significantly higher than in controls. Following saline loading the increment in glomerular filtration rate (GFR) in patients with CF was significantly lower than that of controls. We conclude that patients with CF when subjected to volume expansion demonstrate a lower tubular reabsorptive capacity of sodium as well as a reduced ability to increase their GFR. The defect in sodium reabsorption is probably located in the proximal tubule.

Calcium↗
PubMed1983

Isolation and analysis of melanoma cell mutants resistant to the antiproliferative action of retinoic acid.

Retinoic acid inhibits both the anchorage-dependent and the anchorage-independent growth of the murine melanoma S91-C-2 cells. To explore the mechanism of these effects, several mutant cell clones resistant to retinoic acid-induced growth inhibition have been derived from the S91-C-2 cells by exposing them to the mutagen ethyl methane sulfonate and plating in soft agarose in the presence of 1 microM beta-all-trans-retinoic acid. Under such conditions, the nonmutagenized S91-C-2 cells failed to grow; however, 2 X 10(-6) of the mutagenized cells did form colonies. These colonies were isolated, expanded in culture, and recloned in agarose containing retinoic acid. Five cell clones that retained their drug-resistant phenotype after repeated subculture for 3 months, in the absence of retinoic acid, were characterized further. They were found to be 3- to greater than 1000-fold and 100- to greater than 100-fold resistant to retinoic acid-induced inhibition of anchorage-independent and anchorage-dependent growth relative to the wild-type C-2 cells, respectively. The rate of uptake of [3H]-retinoic acid by the resistant cell clones was similar to that of the sensitive C-2 cells, indicating that resistance is not the result of reduced uptake. Analysis of cytoplasmic retinoic acid-binding protein revealed that it is present in the most resistant clones in amounts that are similar to or even greater than those found in the sensitive S91-C-2 cells. These results indicate that resistance is not the result of the absence of the binding protein. The retinoic acid-resistant mutants exhibited cross-resistance to related retinoids such as 13-cis-retinoic acid and all-trans-retinol as well as to the arotinoid p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) propenyl]benzoic acid suggesting that they all share a similar mechanism of action. These resistant mutants may provide a useful system for further studies of the molecular processes through which retinoic acid exerts its antiproliferative effects.

Animals↗
PubMed1982

Desmopressin in nocturnal enuresis.

The response of desamino-D-arginine vasopressin (DDAVP) was investigated in 32 enuretic children in a double-blind clinical study. The 15 children treated with DDAVP showed a significant reduction in the incidence of bed wetting--from 18.7 +/- 6.5 to 6.5 +/- 9.2 wet nights per 30 days. In 6 children bed wetting stopped entirely, in 6 there was a satisfactory response, and in 3 the response was marginal or there was none. When DDAVP was stopped most children reverted to their earlier bedwetting habits (15.7 +/- 8.9 nights a month). Response to DDAVP was significantly better in children aged more than 10 years (mean age for the entire group). The administration of DDAVP was not associated with any appreciable change in morning urine osmolalities. No adverse effects were noted. It is concluded that DDAVP is effective in nocturnal enuresis, particularly in older children. It is suggested that the cessation of bed wetting may, in part, reflect functional properties of DDAVP rather than antidiuresis.

Adolescent↗
PubMed1981

Characterization of retinoic acid-induced alterations in the proliferation and differentiation of a murine and a human melanoma cell line in culture.

We employ the murine S91 and the human Hs939 melanoma cell lines for the characterization of various biochemical changes induced by retinoids. Retinoic acid (RA) causes a time-dependent, and reversible reduction in cell proliferation rate in liquid medium and inhibits growth in agar. The proportion of cells in the G1 phase of the cell cycle increases in RA-treated cells, and the uptake of TdR, UdR and Leu decreases. The growth inhibitory effect of RA is apparently not mediated via labilization of lysosomes, increase in cAMP or changes in the synthesis of prostaglandins or polyamines. Exposure to RA stimulates tyrosinase activity and increases melanin content severalfold over the levels found in untreated cells. Various retinoids exhibit the activities of RA; however, their potencies vary depending on their structure. Those possessing a free -COOH at C-15 are usually more effective than those with a different group or with a derivatized carboxyl. A positive correlation exists between the ability of retinoids with a free -COOH in C-15 to inhibit growth and to bind to an RA-binding protein found in the S91 melanoma cells. Future studies will explore recently discovered changes in the glycosylation of cell surface components and their relationship to the phenomena described here.

Animals↗
PubMed1981

Enhancement of melanotic expression in cultured mouse melanoma cells by retinoids.

Retinoic acid (RA), which reduces the rate of cell proliferation in S91 mouse melanoma clone C2 cells, was found to stimulate the expression of their melanotic phenotype. RA treatment also induced the extension of long cellular processes. The RA effects on melanogenesis included stimulation of tyrosinase activity and augmentation of cellular melanin content to levels 3- to 4-fold higher than in untreated cultures at similar cell densities. These effects became apparent after 48 hours of exposure to 10(-5) M RA and increased thereafter. Half-maximal stimulation in cells treated for 6 days occurred at 5 X 10(-7) M RA. Although the degrees of melanogenesis enhancement by RA (10(-5) M) and by alpha-melanocyte stimulatory hormone (2 X 10(-7) M) were similar, the former did not alter the intracellular cAMP level, whereas the latter induced a transient 4-fold increase. In high-passage (p28) cells, as well as in low-passage cells (less than p10) treated with tyrosinase inhibitor phenylthiocarbamate, melanin synthesis was suppressed in the absence and presence of RA, yet the ability of RA to inhibit cell proliferation was not compromised. In the presence of the tumor promotor phorbol myristate acetate (greater than 5 X 10(-9) M) melanin synthesis in control as well as in cells exposed to RA was dramatically inhibited. Phorbol which is not active in tumor promotion had no effect on melanogenesis. In addition to RA, other retinoids, such as 13-cis-retinoic acid, retinyl acetate, the TMMP analog of RA and the phenyl analog of RA, but not the pyridyl analog of RA or retinyl palmitate, also inhibited cell growth and enhanced melanin synthesis.

Animals↗