Intracellular pH during mitogenic stimulation induced by alkaline pH.
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Alkalies↗
Biomedical subjects
W Engström
Publications and source records attributed to W Engström.
Mitogenic effect of alkaline pH on quiescent, serum-starved cells.
The effect of environmental pH on the proliferative activity of sparse 3T3 cell cultures was investigated. When quiescent (serum-starved) cells were transferred to a serum-depleted medium in which pH had been elevated, cell proliferation was stimulated during the first 24 hr after the medium change, as reflected by an increase in cell number and in the proportion of cells synthesizing DNA (measured by autoradiography and flow cytophotometry). The growth-stimulatory effect was greater with increasing pH. At pH 8.2 the effect was approximately 50% of that seen in serum-stimulated cells (i.e., upon the addition of 10% serum). Above pH 8.2 toxic effects and cell death were observed. However, the stimulatory effect could be performed without interference of toxic effects by exposing the cells to the high alkaline environment for a short period. A maximum stimulatory effect on the quiescent cells--without any observed toxic effects--was seen after exposure to an alkaline pulse with a duration of 2-10 min at a pH between 8.5 and 10. More than 80% of the cells synthesized DNA during the first 24 hr after the alkaline-pulse stimulation, which is an almost similar response to that seen after stimulation with serum. The growth-stimulatory effect of the alkaline-pulse treatment could not be prevented by a subsequent treatment at acid pH. Kinetic analysis revealed that DNA synthesis was not initiated until 9-12 hr after the alkaline-pulse treatment. This lag period was of the same length as that seen after stimulation with serum. Alkaline-pulse treatment only resulted in stimulation of DNA synthesis and mitosis during one cell cycle. When the alkaline treatment was repeated, only a small proportion of cells could proceed through a second cell cycle.
Animals↗
Urinary excretion of beta 2-microglobulin in myeloma patients.
The levels of beta 2-microglobulin in urine and serum were determined in 39 patients with myelomatosis. In 25 patients the serum beta 2-microglobulin was elevated, and in seven of the patients with increased serum beta-microglobulin the urinary excretion of the protein was also increased. It was concluded that the increased urine beta-microglobulin indicates a renal tubular disorder.
Adolescent↗
Urine B2-microglobulin in patients with macroglobulinemia Waldenström.
The level of B2-microglobulin in the urine was determined by a radioimmunoassay technique in six patients with Waldenström's macroglobulinemia. In 50% of the patients the B2-microglobulin in the urine was significantly increased. In none of the analyzed patients any glomerular malfunction, as measured by serum creatinine and creatinine clearance, was observed.
Aged↗
Transcriptional regulation and biological significance of the insulin like growth factor II gene.
The insulin like growth factors I and II are the most ubiquitous in the mammalian embryo. Moreover they play a pivotal role in the development and growth of tumours. The bioavailability of these growth factors is regulated on a transcriptional as well as on a posttranslational level. The expression of non-signalling receptors as well as binding proteins does further tune the local concentration of IGFs. This paper aims at reviewing how the transcription of the IGF genes is regulated. The biological significance of these control mechanisms will be discussed.
Animals↗
The effects of glycosylation inhibitors on the proliferation of a Wilms tumour cell line.
We have examined the effects of different glycosylation inhibitors on the proliferation of a human Wilms tumour derived cell line WCCS-1. It was found that two compounds that specifically inhibit distal steps in the glycosylation chain (swainsonone and castanospermine) only exerted marginal effects on cell multiplication and survival. In contrast, a proximal inhibitor (tunicamycin) efficiently increased necrosis in a dose dependent fashion. It is shown that this cell death was accompanied by a marked decrease in the incorporation of glucosamine, but rather unexpectedly, only caused a limited inhibition of de novo protein synthesis. Moreover, the entrance into S-phase was virtually unchanged in the cells surviving the exposure to tunicamycin. The effects of tunicamycin on cell multiplication and survival could not be reversed by concomitant addition of mevalonate as has been shown in other cell lines. Taken together this data suggests that tunicamycin does not operate in a cell cycle specific manner in Wilms tumour cells.
Antineoplastic Agents↗
Dual effects of four members of the fibroblast growth factor member family on multiplication and motility in human teratocarcinoma cells in vitro.
The effects of four recently discovered members of the Fibroblast Growth Factor family, FGF-10, FGF-16, FGF-17 and FGF-18, on the human embryonal carcinoma derived cell line Tera 2 were examined. It was found that all four FGF:s enhanced the survival rate of Tera-2 cells by counteracting apoptosis at concentrations in the interval 1-10 ng/ml. When higher concentrations of either of the four FGF:s were added, a preferential effect on cell motility was observed. The observed requirements for externally supplied FGF:s were complemented by the expression of all four FGF-receptors.
Blotting, Northern↗
Local tolerance to spider silks and protein polymers in vivo.
Spider silks were implanted subcutaneously in pigs for a study of the tolerance against this material. Four types of spider silks of high purity and cleanliness were implanted: (i) major ampullate dragline silk reeled from the golden silk spider Nephila clavipes, (ii) native (unsterilised) silk reeled from a Brachypelma spider, (iii) native silk taken from this spider's web and (iv) its web silk thermally treated at 80 degrees C. For comparison we used fibrous silk analogue protein polymers and four already marketed wound dressings (polyurethane film, collagen dressings, gauze pads). All materials were applied epicutaneously to split skin wounds. The implants were examined macroscopically as well as by light microscopy. Superficially, all sites healed rapidly. There were marked inflammatory reactions in all sites with lympho-plasmacellular infiltrations, evidence of phagocytosis and granuloma formation as indicated by the appearance of giant cells. However there was a marked absence of epitheloid cells indicating that the observed reaction was a foreign body granuloma. Furthermore, the histopathological images recorded after 14 days revealed no marked differences between the dressings. Polyurethane films, however, seemed to be superior with respect to the duration of the wound healing process.
Animals↗
Expression of the 3-hydroxy-3-methylglutaryl coenzyme A-reductase and LDL-receptor genes in human embryonic tumours and in normal foetal tissues.
The expression of the HMG-CoA-reductase and LDL-receptor genes was examined in primary human embryonic tumours and in normal human first trimester foetal tissues. All embryonic and extra-embryonic tissues examined contained RNA that hybridized with the HMG-CoA-reductase and LDL-receptor cDNA-probes. However, the transcript levels varied considerably between organs. By using Northern blotting, we confirmed that normal foetal tissues contained HMG-CoA-reductase and LDL-receptor transcripts of normal size (4.2 kB and 5.3 kB, respectively). All human developmental tumours examined were characterized by high levels of HMG-Co-A-reductase RNA. However, when the quality of this RNA was examined in greater detail it was found that the 4.2 kB band only accounted for a minor portion of the RNA. Instead we found a range of other transcripts (3.1, 1.1., 0.95, 0.78 and 0.55 kB) that hybridized with the probe. There was a qualitative difference in that only the non-seminomas contained high levels of the three smaller transcripts (0.95, 0.78 and 0.55 kB). In contrast, only one tumor--an embryonal carcinoma--contained increased levels of LDL-receptor transcript. This was found to be of the expected size (5.3 kB).
Cell Division↗
Expression of c-myc in canine mammary tumours.
The expression of the protooncogene c-myc was examined in twelve canine mammary tumours of different histological type. Only in one tumour--a poorly differentiated carcinoma--was the amount of RNA that hybridized with our cDNA probe for the myc gene significantly increased. Restriction fragment length analysis of genomic DNA from this tumour did not reveal any amplification or other rearrangements in this gene locus.
Animals↗
Expression of the myc protooncogene in canine rhabdomyosarcoma.
The expression of the protooncogene c-myc in a canine rhabdomyosarcoma was examined. It was found that this highly malignant tumour contained vast quantities of RNA that hybridized with a cDNA probe for c-myc. Restriction fragment length analysis after endonuclease digestion of tumour DNA did not reveal any rearrangements in this gene locus. The potential role of this oncogene in the development of canine rhabdomyosarcoma is discussed.
Animals↗
The biological effects of a high molecular weight form of IGF II in a pluripotential human teratocarcinoma cell line.
The human teratoma cell line Tera 2 synthesizes and secretes insulin like growth factors into the culture medium. Size fractionation of conditioned medium by acidic gel filtration chromatography showed that the medium contains the canonical 7 kD IGF II, as well as a large IGF II variant, immunologically crossreactive with canonical IGF II. Amino acid analysis of the Tera 2 secreted large IGF II variant has shown that it is biochemically distinct from previously isolated high molecular weight variants of IGF II. Both species of IGF II support cell multiplication of Tera 2 cultures, albeit with different potency. In spite of the resulting potential for autocrine growth of Tera 2, we failed to observe such a situation. We propose that one reason for this failure to observe such a situation. We propose that one reason for this failure is the co-secretion of the 29 kD IGF binding protein type 1 with IGF II, which we have demonstrated to inhibit the biological effects of the growth factor on Tera 2 cells.
Carrier Proteins↗